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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Glial tumours are the most common primary tumours of the central nervous system &#40;CNS&#41;&#46; Glioblastoma is the most aggressive primary brain tumour and has the highest incidence &#40;2&#46;96 individuals per 100&#44;000 population&#41;&#44; followed by anaplastic astrocytoma &#40;0&#46;49 per 100&#44;000 population&#41;&#44; oligodendroglioma &#40;0&#46;34 per 100&#44;000 population&#41;&#44; diffuse astrocytoma &#40;0&#46;13 per 100&#44;000 population&#41; and anaplastic oligodendroglioma &#40;0&#46;10 per 100&#44;000 population&#41;&#46; The survival of these patients depends on the type of tumour&#46; The most deadly is glioblastoma&#44; with a five-year survival rate of 3&#37;&#44; followed by anaplastic astrocytoma&#44; with a five-year survival rate of 28&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">1&#8211;4</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">To assess the survival of these patients&#44; prognostic factors such as tumour size&#44; age&#44; extent of resection or cell lineage have been reported&#46; The following useful molecular markers can be added in the diagnosis of gliomas&#58; MGMT&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">5</span></a> isocitrate dehydrogenase &#40;IDH&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">6&#44;7</span></a> 1p&#47;19q co-deletion<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">8&#44;9</span></a> or p53&#44; known for influencing the natural history and prognosis of these tumours&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">3&#44;5&#44;10&#8211;12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2016&#44; the World Health Organization &#40;WHO&#41; published the new classification of tumours of the CNS&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> which shows a series of substantial changes with respect to the previous classification from 2007&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> The most significant change is the use of molecular genetic markers&#44;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">12</span></a> with genetic data appearing for the first time in the naming of glial tumours &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; This new classification of gliomas is determined by the mutation status of the IDH gene &#40;IDH1 most common or IDH2&#41; and the presence or absence of the 1p&#47;19q co-deletion&#44; making it possible to differentiate astrocytomas according to the IDH mutation status&#44; mutated or not mutated &#40;wild type&#41;&#44; and to diagnose as oligodendrogliomas tumours in which the co-deletion and the mutated IDH gene are present&#46; The term NOS &#40;not otherwise specified&#41; is introduced to indicate gliomas in which it has not been possible to carry out this molecular testing&#44; or in which this testing has not been conclusive&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Therefore&#44; new diagnostic codes are introduced according to molecular genetics and morphology&#58; diffuse astrocytoma&#44; IDH-mutant&#47;wild type or NOS&#59; glioblastoma&#44; IDH mutant&#47;wild type or NOS&#59; oligodendroglioma&#44; IDH-mutant and with 1p&#47;19q co-deletion or NOS&#44; etc&#46; With this new classification&#44; the former diagnosis of oligoastrocytoma disappears&#46; Despite the importance of genetics&#44; histopathology is not neglected&#44; as it is the first step to define the type of tumour and its grade of aggressiveness&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">13&#44;15&#44;16</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Taking into account this major change&#44; the possibility that there are several diagnostic changes in these tumours is raised&#44; generating doubts regarding the prognosis and the treatment of the patients&#46; The objective of this paper was to analyse and evaluate the impact caused by the change in the diagnosis of gliomas using this new classification in a series of cases diagnosed at our centre&#44; based on epidemiological&#44; therapeutic and prognostic variables&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">This was a retrospective analysis of 147 cases of glial tumours in patients treated at the Hospital General Universitario Gregorio Mara&#241;&#243;n &#91;Gregorio Mara&#241;&#243;n General University Hospital&#93; in Madrid&#46; Within this sample&#44; the cases were selected with diagnostic review when molecular testing was introduced in comparison with the previous morphological diagnosis&#46; This study was approved by the Ethics Committee of the Hospital Gregorio Mara&#241;&#243;n &#40;study code OMSGC-2017&#41;&#44; respecting the basic ethical principles and standards that are derived from the current revision &#40;revised version from Fortaleza&#44; 2013&#41; of the Declaration of Helsinki approved by the World Medical Association&#44; the Oviedo Convention and the current regulatory requirements listed in Spanish legislation&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The inclusion criteria were as follows&#58; patients diagnosed with a primary brain tumour in the Hospital General Universitario Gregorio Mara&#241;&#243;n in whom tumour resection surgery or a diagnostic biopsy was performed between January 2012 and June 2016&#44; with a diagnosis of tumours of astrocytic or oligodendroglial lineage&#44; with a complete medical history and with a minimum follow-up of six months&#46; The cases in which a glial tumour was diagnosed were reviewed in the histological study&#44; and molecular genetic testing was performed by studying the IDH mutations and the presence&#47;absence of 1p&#47;19q co-deletion&#46; The IDH1 mutation was analysed using immunohistochemistry techniques&#44; and sequencing of the IDH gene may have been performed with polymerase chain reaction &#40;PCR&#41; in those patients with negative IDH who were highly suspected of being carriers of the mutation due to low grade or oligodendroglial lineage in the histological study&#46; In contrast&#44; the 1p&#47;19q co-deletion was studied using fluorescence in situ hybridisation &#40;FISH&#41; techniques&#46; In those situations in which it was not possible to obtain a result from the study &#40;deceased patients or impossibility of performing the 1p&#47;19q co-deletion study&#41;&#44; or if the result was not conclusive&#44; the diagnosis of glioma NOS was given&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The epidemiological variables collected in the study were age of the patients and gender&#59; the therapeutic variables were the type of surgical treatment &#40;surgical resection or diagnostic biopsy&#41; and the complementary treatment &#40;conservative&#44; radiotherapy&#44; radiotherapy and chemotherapy or chemotherapy alone&#41;&#44; and the prognostic variables were the tumour grade&#44; the glial lineage&#44; the presence of the IDH mutation&#44; the presence of the 1p&#47;19q co-deletion&#44; the date of diagnosis and the date of death&#46; The cases in which the initial histological diagnosis changed after the application of molecular genetics were collected&#46; The extent of resection or the radiological variables of surgical resection were not studied&#44; given that it was not an objective of this study&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Regarding the statistical analysis&#44; this was performed with the IBM SPSS Statistics 24&#46;0 program&#46; For the qualitative variables&#44; the Chi-square test<span class="elsevierStyleSup">2</span> or the Fisher&#39;s exact test was used&#46; The analysis of survival was performed with Kaplan&#8211;Meier curves&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">In this study&#44; data were collected from 147 patients with glial tumours who underwent operations during the period from 1 January 2012 to 30 June 2016 &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; In this series&#44; 52&#37; of patients were male and 48&#37; female&#44; with the median overall age being 56 &#40;1&#8211;81&#41;&#44; and with more than 85&#37; of the patients over the age of 40&#46; After the analysis of 147 cases by initial histological study&#44; the following results were obtained&#58; 3 &#40;2&#37;&#41; ependymomas&#44; 11 &#40;7&#46;5&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> astrocytomas&#44; 20 &#40;13&#46;6&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span> astrocytomas&#44; 25 &#40;17&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> oligodendrogliomas&#44; 10 &#40;6&#46;8&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span> oligodendrogliomas and 78 &#40;53&#46;1&#37;&#41; glioblastomas &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Of these patients&#44; the molecular diagnosis was obtained in 74 cases &#40;50&#46;3&#37;&#41;&#58; 3 &#40;4&#37;&#41; ependymomas&#44; 6 &#40;8&#46;1&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> astrocytomas&#44; 20 &#40;27&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> oligodendrogliomas&#44; 7 &#40;9&#46;5&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span> astrocytomas&#44; 7 &#40;9&#46;5&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span> oligodendrogliomas and 31 &#40;41&#46;9&#37;&#41; glioblastomas&#44; with the remainder of the cases diagnosed as gliomas NOS &#40;73 cases&#59; 49&#46;7&#37;&#41; due to the impossibility of performing genetic testing or when this was considered inconclusive&#58; 5 diffuse astrocytomas NOS&#44; 13 anaplastic astrocytomas NOS&#44; 5 oligodendrogliomas NOS&#44; 3 anaplastic oligodendrogliomas NOS and 47 glioblastomas NOS&#46; Out of all the cases studied&#44; the analysis of the IDH1 mutation was obtained in 95 tumours &#40;64&#46;62&#37;&#41; and the analysis of the 1p&#47;19q co-deletion was obtained in 66 tumours &#40;44&#46;89&#37;&#41;&#46; Of the 74 glial tumours in which complete genetic testing was performed&#44; in 23 cases &#40;31&#37;&#41; the diagnosis changed&#44; with the histological diagnosis of oligodendroglioma predominating in 20 patients &#40;87&#37;&#41; as an initial histological diagnosis &#40;69&#46;6&#37; grade <span class="elsevierStyleSmallCaps">ii</span> and 17&#46;4&#37; grade <span class="elsevierStyleSmallCaps">iii</span>&#41;&#44; and with these 20 cases becoming astrocytomas&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">In summary&#44; after applying genetic testing in these 74 patients&#44; the following changes were obtained in the molecular diagnosis&#58; 3 &#40;2&#37;&#41; ependymomas&#44; 21 &#40;14&#46;3&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> astrocytomas&#44; 11 &#40;7&#46;5&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span> astrocytomas&#44; 5 &#40;3&#46;4&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> oligodendrogliomas&#44; 5 &#40;3&#46;4&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span> oligodendrogliomas and 29 &#40;19&#46;7&#37;&#41; glioblastomas &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The statistical analysis was performed with all the patients who underwent complete genetic testing &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>74&#41;&#44; in whom the diagnosis changed on 23 occasions &#40;31&#37;&#41;&#46; Of these tumours 20 &#40;87&#37;&#41; were diagnosed initially as oligodendrogliomas&#44; with 16 &#40;69&#46;6&#37;&#41; classified as grade <span class="elsevierStyleSmallCaps">ii</span> and 4 &#40;17&#46;4&#37;&#41; grade <span class="elsevierStyleSmallCaps">iii</span>&#46; All the oligodendrogliomas which changed diagnosis were re-diagnosed as astrocytomas&#46; The three remaining tumours corresponded to two &#40;8&#46;7&#37;&#41; glioblastomas which became grade <span class="elsevierStyleSmallCaps">iii</span> oligodendrogliomas and one &#40;4&#46;3&#37;&#41; grade <span class="elsevierStyleSmallCaps">ii</span> astrocytoma which became a grade <span class="elsevierStyleSmallCaps">ii</span> oligodendroglioma with the new classification&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">When we evaluated the change of diagnosis of the glial tumours in relation to the epidemiological variables&#44; a trend of a greater change of diagnosis was obtained in young patients &#40;&#60;40&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;065&#44; mainly with a previous diagnosis of oligodendroglioma&#44; and with no statistically significant relationship to gender&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">With regard to the relationship between molecular findings and frequency of diagnostic change&#44; of the 23 cases in which the diagnosis changed&#44; IDH1 was positive on 16 occasions &#40;69&#46;6&#37;&#41;&#44; in a statistically significant manner &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#41;&#44; and the 1p&#47;19q co-deletion was negative on 20 occasions &#40;87&#37;&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; Regarding cell lineage&#44; in our series&#44; of the 27 oligodendrogliomas detected with molecular testing&#44; 20 &#40;74&#37;&#41; changed diagnosis due to having negative co-deletion&#44; becoming astrocytomas&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">With regard to the treatment variables in the series analysed &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>74&#41;&#44; we observed that the surgical treatment received in this group of patients was neuronavigation-guided biopsy in 10 cases &#40;13&#46;51&#37;&#41; and surgical resection in 64 cases &#40;86&#46;48&#37;&#41;&#46; On the other hand&#44; the complementary treatment received was&#58; conservative in 16 cases &#40;21&#46;62&#37;&#41;&#44; holocranial radiotherapy in 17 cases &#40;22&#46;97&#37;&#41; concomitant radiotherapy and chemotherapy in 40 cases &#40;54&#46;05&#37;&#41; and chemotherapy alone in one case &#40;0&#46;01&#37;&#41;&#46; In addition&#44; the treatment of the subgroup of patients in whom the diagnosis changed &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#41; was surgical resection on 23 occasions &#40;100&#37;&#41;&#44; followed by conservative treatment in 7 &#40;30&#46;43&#37;&#41;&#44; holocranial radiotherapy in 8 &#40;34&#46;78&#37;&#41; and concomitant radiotherapy and chemotherapy in 8 &#40;34&#46;78&#37;&#41;&#46; No significant variations were obtained with regard to treatment&#46; This was probably due to the small sample size&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Finally&#44; in relation to survival&#44; a Kaplan&#8211;Meier curve was performed &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#44; with a mean follow-up of 16 months&#44; in which a mean survival of 1046 days was obtained in patients in whom the diagnosis was changed by molecular testing and&#44; on the other hand&#44; a mean survival of 654 days was observed in those in whom the diagnosis did not change &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#46; Taking into account the mean survival by histological grade&#44; no significant differences were observed between the tumours with or without a change in diagnosis&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> describes the mean survival times for each histological group in relation to the presence of a change in diagnosis&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The new WHO classification of tumours of the CNS issued in 2016<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> is the greatest change in the diagnosis of gliomas since the first WHO classification in 1979&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> and obliges neuro-oncologists to manage new concepts of molecular genetics&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Throughout history&#44; the classification of CNS tumours has had different approaches in accordance with the medical-surgical and histological knowledge of the time&#46; The first classification&#44; described in 1926&#44; was that of Bailey and Cushing&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">18</span></a> which was based on prognostic variables of survival for each histological tumour type of the nervous system&#46; Subsequently&#44; other notable classifications were developed&#44; such as that of Kernohan<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">19</span></a> &#40;1949&#41;&#44; which started to differentiate tumours into four grades according to their grade of aggressiveness&#44; or that of St&#46; Anne-Mayo<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">20&#44;21</span></a> &#40;1988&#41;&#44; which differentiated astrocytomas and oligodendrogliomas into grades based on four histological parameters&#58; mitosis&#44; atypia&#44; necrosis and neovascularisation&#46; Based on previous classifications&#44; the WHO created its own classification in 1979<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">17</span></a> and has been adding changes into its successive publications in 1993&#44;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">22</span></a> 2000&#44;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">23</span></a> 2007<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">14</span></a> and up to the most recent publication&#44; in 2016&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">The most relevant change in this new 2016 classification is the addition of molecular genetics&#46; Additionally&#44; there are some conceptual changes with regard to the cellular subtypes of astrocytomas and ependymomas&#44; and some specific changes&#44; such as the disappearance of <span class="elsevierStyleItalic">gliomatosis cerebri</span> as a tumour subtype&#44; considering it from now on as a type of tumour growth of the different subtypes of gliomas&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Taking into account all of the changes incorporated&#44; an algorithm &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41; to follow is established in order to correctly define a glial tumour&#44; using molecular genetics&#46; This algorithm means that the presence of mixed glial tumours &#40;oligoastrocytomas&#41; is substantially reduced&#44; although it also implies that in the centres in which there is difficulty reaching a diagnosis&#44; or in which it is not possible to analyse any mutation&#44; the glial tumour is described as NOS&#46; This algorithm starts with the histological study of the glial lineage prior to the detection of mutations &#40;IDH1 or 1p&#47;19q co-deletion&#41;&#44; those most known in relation to this type of tumour&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The first mutated gene which was associated with gliomas was IDH&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">6&#44;24&#44;25</span></a> This gene&#44; a cellular oncometabolite that&#44; when it is mutated&#44; inhibits alpha-ketoglutarate-dependent enzymes&#44; has an important role in the epigenetic profile of the cell&#44; inhibits differentiation and stimulates tumourigenesis&#46; The relationship between IDH1 and IDH2 mutations has been demonstrated with low-grade glial tumours and secondary glioblastomas&#44; with the IDH1 mutation being the most common&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Other genes&#44; such as alpha thalassemia <span class="elsevierStyleSmallCaps">X</span>-linked mental retardation syndrome &#40;ATRX&#41;&#44; are also associated with gliomas&#46; ATRX<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a> regulates the remodelling of chromatin and encodes a protein which is found in endothelial cells&#44; cortical neurons and inflammatory cells&#46; When this gene is mutated&#44; no expression of the protein is observed in immunohistochemistry &#40;<a class="elsevierStyleCrossRef" href="#fig0020">Fig&#46; 4</a>&#41;&#44; and it is associated with tumours of astrocytic origin&#46; Currently&#44; the mutation in the ATRX gene is still not considered necessary for the diagnosis of astrocytomas&#44; but in many centres&#44; such as ours&#44; it is being analysed with increasing frequency&#46; Nevertheless&#44; it is important to highlight that the mutation in the ATRX gene excludes the 1p&#47;19q co-deletion which is present in oligodendrogliomas&#46;</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">It is important to highlight that genetics has managed to associate certain mutations with some types of gliomas&#44; which helps us to categorise them correctly&#44; as is the case of the RELA fusion-positive ependymoma or the diffuse midline glioma with the H3 K27M mutation&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">This study tries to analyse in depth the role of the introduction of molecular genetics for the diagnosis of certain types of brain gliomas&#44; with the objective of improving targeted cancer therapy for these patients in the future&#46; Using this molecular classification&#44; we can distinguish possible causes for variations in the expected survival for certain astrocytomas or oligodendrogliomas which have been incorrectly diagnosed&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> It is suggested that the field in which the application of genetics may be most useful is in low-grade tumours&#44;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">29&#44;30</span></a> as&#44; despite the fact that they are not benign&#44; adequate&#44; well-focused and early treatment may increase the mean survival time&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">31&#44;32</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">For this reason&#44; it has been observed that the genotype enables an improved prognostic classification and a consequent adaptation of treatment&#46; Multiple studies have demonstrated that further development is expected in the field of molecular genetics&#44; through the use of markers other than IDH1 and 1p&#47;19q co-deletion&#44; such as the aforementioned ATRX&#44;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">28</span></a> EGFR&#44; polysomy 7&#44; 10q deletion&#44; TERT prom&#44; BRAF&#44; PTEN and H3F3A&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">11&#44;33</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">In our study&#44; we obtained a greater tendency for a change of morphological diagnosis in young patients &#40;&#60;40 years&#41; at the expense of IDH1-positivity and 1p&#47;19q co-deletion-negativity&#46; Furthermore&#44; we have observed that the greatest change in diagnosis was obtained in patients with initial oligodendroglioma&#44; in particular low grade&#44; due to obtaining negative 1p&#47;19q co-deletion&#44; despite the morphology being more typical of oligodendroglioma&#46; Regarding patients&#8217; prognosis&#44; it is observed in this series that patients with glial tumours which change diagnosis have a longer survival period&#46; However&#44; taking into account that the tumours in which the diagnosis did not vary are mostly high-grade tumours &#40;glioblastomas&#41;&#44; we can conclude that these data are not clinically relevant&#46; In addition&#44; in terms of the survival analysis by histological subgroups&#44; no significant differences were obtained between tumours with a diagnostic change and those without a diagnostic change&#46; Therefore&#44; particularly due to the limited sample size and the short follow-up for this type of condition&#44; we do not observe any differences in the survival rate in this study after the change in diagnosis&#46; Despite this&#44; it is interesting to note that the majority of glial tumours which have a change in diagnosis are oligodendrogliomas&#44; and that&#44; despite becoming astrocytomas&#44; at least in the established follow-up&#44; the improved prognosis of the former is maintained&#46; On the other hand&#44; it has been reported that patients diagnosed with glioblastoma multiforme have a lower incidence and a lower survival rate after changes to the diagnosis due to the new classification&#44; as&#44; with the help of molecular genetics&#44; the number of incorrectly diagnosed glial tumours is decreasing&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">5&#44;34</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">In terms of this study&#39;s limitations&#44; the following factors stand out&#58; the absence of significance in relation to many of the variables analysed&#44; probably due to the small sample and to the limited follow-up that we have for these tumours&#59; the non-randomisation in the selection of patients and the retrospective nature of the study&#46; These factors are due&#44; above all&#44; to the fact that the use of this classification and of the molecular genetics techniques to carry it out&#44; have only started very recently&#46; Moreover&#44; the analysis in greater depth of clinical variables and of treatment &#40;extent of resection&#44; radiotherapy and chemotherapy treatment regimens&#44; disease-free survival&#44; re-treatments&#44; among others&#41; may allow for a greater knowledge to be gained of the impact of tumours with discordant histology and molecular findings&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conclusions</span><p id="par0145" class="elsevierStylePara elsevierViewall">In our experience&#44; the new WHO classification of tumours of the CNS<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a> using molecular genetics is a major breakthrough which has generated a new clinical framework&#46; The detection of glial tumours with morphological patterns of one lineage and discordant molecular findings has involved diagnostic reclassifications of a considerable percentage of glial tumours in which this has been reviewed&#46; In this study&#44; the main finding in reclassified tumours has been the absence of 1p&#47;19q co-deletion in most initial oligodendrogliomas&#44; which leads to the change to astrocytomas&#46; In addition&#44; a tendency to a greater frequency of this change of diagnosis has been detected in younger patients and in low-grade gliomas&#46; In any case&#44; the limited sample size and the short follow-up prevents more in-depth conclusions in this phase of the study&#46; However&#44; this study forms part of a more complete study with an extended follow-up period to evaluate possible prognostic conclusions and therapeutic implications&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors state that there are no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The aim of this project is to assess diagnostic reclassification based on molecular data over morphology in a series of glial tumours since the introduction of the 2016 WHO classification of brain tumours&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Retrospective review of glial tumours &#40;oligodendrogliomas and astrocytomas&#41; treated in our centre between January 2012 and June 2016 in which a review of diagnosis was performed when molecular studies were added&#46; Statistical analysis included evaluation of variables of epidemiology&#44; morphology and molecular data &#40;mainly IDH mutation and 1p19q codeletion&#41;&#44; diagnostic changes after new classification was considered&#44; and clinical impact in cases of diagnostic reclassification&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">From a total of 147 glial tumours reviewed in our centre&#44; molecular diagnosis was obtained in 74 cases &#40;50&#46;3&#37;&#41;&#46; Initial diagnosis changed in 23 cases &#40;31&#37;&#41;&#44; and 20 &#40;87&#37;&#41; of them had a prior histological diagnosis of oligodendroglioma &#40;69&#46;6&#37; grade <span class="elsevierStyleSmallCaps">ii</span> and 17&#46;4&#37; grade <span class="elsevierStyleSmallCaps">iii</span>&#41;&#46; Only 3 of these 23 cases diagnosis changed from astrocytoma to oligodendroglioma&#46; Among reclassified tumours&#44; there was a common molecular pattern&#44; as findings showed mutant IDH in 16 cases &#40;69&#46;6&#37;&#41; and no codeletion in 20 cases &#40;87&#37;&#41;&#46; According to the cell of origin&#44; of the whole group of 27 oligodendrogliomas in our series &#40;reclassified and non-reclassified&#41;&#44; 20 cases &#40;74&#37;&#41; became astrocytomas&#44; despite typical oligodendroglial morphology&#44; due to absence of 1p19q codeletion&#46; There was a trend for diagnosis reclassification in younger patients &#40;&#60;40 years&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;065&#44; mainly in those with a prior diagnosis of oligodendroglioma&#44; with no statistical differences based on gender or clinical data&#46; Besides&#44; reclassification was more common among tumours with mutant IDH &#40;69&#46;6&#37;&#41;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003&#44; than those with wild type IDH&#46; In terms of survival&#44; despite receiving different treatments&#44; no significant changes were detected between reclassified and non-reclassified tumours after a mean follow-up of 16 months&#44; partly related to lower grade of these lesions&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Within the spectrum of the glial tumours treated in our institution&#44; this new classification including molecular genetics over morphological data has provided marked diagnostic changes&#46; These changes appear mainly in tumours previously diagnosed as oligodendrogliomas and in younger patients&#44; with molecular patterns of mutant IDH and 1p19q codeletion&#46; Although diagnosis reclassification may affect clinic&#44; prognosis or therapeutic management of these tumours&#44; deeper and prospective studies on these specific aspects are needed&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background and objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este trabajo es evaluar el cambio del diagn&#243;stico molecular sobre el histol&#243;gico de una serie de tumores gliales al revisar el diagn&#243;stico con la clasificaci&#243;n de la OMS de 2016&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materiales y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realiza un estudio retrospectivo de los tumores gliales &#40;oligodendrogliomas y astrocitomas&#41; tratados en nuestro centro entre enero de 2012 y junio de 2016&#44; y una revisi&#243;n diagn&#243;stica seg&#250;n su estudio molecular&#46; Se lleva a cabo el an&#225;lisis estad&#237;stico de variables epidemiol&#243;gicas&#44; histol&#243;gicas y de gen&#233;tica molecular &#40;mutaciones en IDH y presencia de codeleci&#243;n 1p19q&#41;&#44; variaci&#243;n en el diagn&#243;stico al introducir la nueva clasificaci&#243;n tumoral e impacto cl&#237;nico de dicha reclasificaci&#243;n&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">De los 147 casos de tumores gliales revisados&#44; se obtuvo el diagn&#243;stico molecular en 74 casos &#40;50&#44;3&#37;&#41;&#46; En 23 casos &#40;31&#37;&#41; cambi&#243; el diagn&#243;stico&#44; predominando en 20 &#40;87&#37;&#41; el diagn&#243;stico previo de oligodendroglioma &#40;69&#44;6&#37; grado <span class="elsevierStyleSmallCaps">ii</span> y 17&#44;4&#37; grado <span class="elsevierStyleSmallCaps">iii</span>&#41;&#46; Solo 3 de los 23 casos cambiaron de diagn&#243;stico inicial astrocitario al oligodendroglial&#46; Respecto al patr&#243;n molecular en estos 23 casos&#44; se detect&#243; IDH mutado en 16 &#40;69&#44;6&#37;&#41; y codeleci&#243;n 1p19q negativa en 20 &#40;87&#37;&#41;&#46; Seg&#250;n la estirpe celular&#44; de los 27 oligodendrogliomas de esta serie&#44; 20 &#40;74&#37;&#41; cambiaron de diagn&#243;stico por tener la codeleci&#243;n negativa&#44; pasando a ser astrocitomas&#46; Se observ&#243; una tendencia a un mayor cambio de diagn&#243;stico en pacientes j&#243;venes &#40;&#60;40 a&#241;os&#41;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;065&#44; mayoritariamente con diagn&#243;stico previo de oligodendrogliomas&#44; sin relaci&#243;n con el sexo&#46; Adem&#225;s&#44; se detect&#243; una mayor frecuencia de cambio de diagn&#243;stico entre los tumores con IDH mutado &#40;69&#44;6&#37;&#41;&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;003&#46; Respecto a la supervivencia o el patr&#243;n cl&#237;nico&#44; no se detectaron cambios significativos entre los tumores con o sin cambio diagn&#243;stico&#44; a pesar de no recibir tratamiento de elecci&#243;n&#44; tras un seguimiento medio de 16 meses&#44; en probable relaci&#243;n con el bajo grado lesional&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Dentro del espectro de tumores astrocitarios y oligodendrogliales en nuestro centro&#44; la clasificaci&#243;n diagn&#243;stica con gen&#233;tica molecular evidencia importantes cambios respecto al diagn&#243;stico morfol&#243;gico&#46; Estos cambios afectan especialmente a los diagn&#243;sticos previos de oligodendrogliomas y a los pacientes j&#243;venes en los casos revisados&#44; y con patrones moleculares de mutaci&#243;n en la IDH y de ausencia de codeleci&#243;n 1p19q&#46; Si bien se pueden plantear dudas respecto a la cl&#237;nica&#44; el pron&#243;stico y el tratamiento realizado en estos casos&#44; se requieren estudios espec&#237;ficos en estos aspectos para lograr unas conclusiones apropiadas&#46;</p></span>"
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            "identificador" => "abst0030"
            "titulo" => "Materiales y m&#233;todos"
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          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
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        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Valera-Mel&#233; M&#44; Mateo Sierra O&#44; Sola Vendrell E&#44; Guzm&#225;n de Villoria L JA&#44; Carvajal D&#237;az L&#44; Gil de Sagredo del Corral &#211;L&#44; et al&#46; Evaluaci&#243;n del impacto del cambio diagn&#243;stico de los gliomas aplicando la nueva clasificaci&#243;n de la OMS de 2016 sobre una serie de casos&#46; Neurocirugia&#46; 2019&#59;30&#58;19&#8211;27&#46;</p>"
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        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Louis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">13</span></a>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Diagnostic algorithm of the new 2016 WHO classification of gliomas&#46;</p>"
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          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Flow diagram of patients diagnosed with glial tumours in the period between January 2012 and June 2016&#46; Application of the new WHO classification from 2016&#46; &#40;1&#41; Patients in whom complete molecular testing was performed by studying IDH1 mutation and 1p&#47;19q co-deletion&#46; &#40;2&#41; Molecular tests not performed or not conclusive&#46; &#40;3&#41; Oligodendroglioma as the final diagnosis after the application of genetic testing&#46; NOS&#58; not otherwise specified&#59; OLIGO&#58; oligodendroglioma&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Kaplan&#8211;Meier curve survival analysis&#46; Mean survival time of 654 days in patients in whom the diagnosis did not change and 1046 days in patients in whom the diagnosis did change&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#46;</p>"
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          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Histological and immunohistochemistry images of a patient diagnosed histologically with astrocytoma grade <span class="elsevierStyleSmallCaps">ii</span>&#44; reclassified as oligodendroglioma grade <span class="elsevierStyleSmallCaps">ii</span> after detecting 1p&#47;19q co-deletion&#46; Haematoxylin&#8211;eosin with typical astrocytic pattern&#44; ATRX negative&#44; IDH1-mutant&#44; Ki-67 of 1&#37;&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">NOS&#58; not otherwise specified&#59; WHO&#58; World Health Organization&#46;</p><p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Relationship of all patients of the series &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>147&#41; with gliomas with histological diagnosis and molecular diagnosis after applying molecular testing by studying IDH mutation and 1p&#47;19q co-deletion&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tumour&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Histological diagnosis <br>&#40;WHO 2007&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Molecular diagnosis <br>&#40;WHO 2016&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ependymoma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3 &#40;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Astrocytoma grade <span class="elsevierStyleSmallCaps">ii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;7&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">21 &#40;14&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Astrocytoma grade <span class="elsevierStyleSmallCaps">iii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20 &#40;13&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11 &#40;7&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oligodendroglioma grade <span class="elsevierStyleSmallCaps">ii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25 &#40;17&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;3&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oligodendroglioma grade <span class="elsevierStyleSmallCaps">iii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10 &#40;6&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5 &#40;3&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glioblastoma multiforme&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">78 &#40;53&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29 &#40;19&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glioma&#44; NOS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">73 &#40;49&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">147&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison between histological and molecular diagnosis in our series &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>147&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">WHO&#58; World Health Organization&#46;</p><p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">Patients with glial tumours whose diagnosis changed after genetic testing &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#41;&#46; 87&#37; of the tumours for which the diagnosis changed were previously considered oligodendrogliomas&#44; with 69&#46;6&#37; grade <span class="elsevierStyleSmallCaps">ii</span> and 17&#46;4&#37; grade <span class="elsevierStyleSmallCaps">iii&#46;</span></p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Histological diagnosis &#40;WHO 2007&#41;</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Molecular diagnosis<br>&#40;WHO 2016&#41;</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Astrocytoma grade <span class="elsevierStyleSmallCaps">ii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Astrocytoma grade <span class="elsevierStyleSmallCaps">ii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;69&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oligodendroglioma grade <span class="elsevierStyleSmallCaps">ii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16 &#40;69&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oligodendroglioma grade <span class="elsevierStyleSmallCaps">ii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oligodendroglioma grade <span class="elsevierStyleSmallCaps">iii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;17&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Oligodendroglioma grade <span class="elsevierStyleSmallCaps">iii</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;8&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glioblastoma multiforme&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2 &#40;8&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Glioblastoma multiforme&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 &#40;17&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Total change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Diagnostic changes observed in 23 cases of glial tumours&#46;</p>"
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          "leyenda" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Evaluation of the diagnostic change of glial tumours in relation to the molecular study performed&#58; detection of IDH1 mutation and presence&#47;absence of 1p&#47;19q co-deletion&#46;</p>"
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">IDH&#44; co-deletion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnostic change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IDH-mutant&#47;wild type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">69&#46;6&#47;30&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;003</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No diagnostic change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">IDH-mutant&#47;wild type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;5&#47;72&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnostic change&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1p&#47;19q co-deletion &#43;&#47;&#8722;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#47;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="2" align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No diagnostic change&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0110" class="elsevierStyleSimplePara elsevierViewall">Astro&#58; astrocytoma&#59; Epend&#58; ependymoma&#59; GBM&#58; glioblastoma&#59; Oligo&#58; oligodendroglioma&#59; SV&#58; survival&#46;</p><p id="spar0115" class="elsevierStyleSimplePara elsevierViewall">Mean survival times of the 74 glial tumours which underwent genetic testing stratified by glial subtype and histological grades&#46;</p>"
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                0 => """
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">No diagnostic change</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Diagnostic change</th><th class="td" title="table-head  " align="center" valign="top" scope="col">Significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Histology&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">659&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">544&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oligo <span class="elsevierStyleSmallCaps">II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1089&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1163&#46;44&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;302&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Astro <span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">148&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oligo <span class="elsevierStyleSmallCaps">III</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1141&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">365&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;221&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">GBM&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">466&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">221&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;086&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epend&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1066&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0105" class="elsevierStyleSimplePara elsevierViewall">Survival by histological grade of the 74 glial tumours which underwent genetic testing&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:34 [
            0 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology and etiology of gliomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46; Ohgaki"
                            1 => "P&#46; Kleihues"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00401-005-0991-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Neuropathol"
                        "fecha" => "2005"
                        "volumen" => "109"
                        "paginaInicial" => "93"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15685439"
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                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Changing incidence and improved survival of gliomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
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                            0 => "V&#46;K&#46;Y&#46; Ho"
                            1 => "J&#46;C&#46; Reijneveld"
                            2 => "R&#46;H&#46; Enting"
                            3 => "H&#46;P&#46; Bienfait"
                            4 => "P&#46; Robe"
                            5 => "B&#46;G&#46; Baumert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejca.2014.05.019"
                      "Revista" => array:6 [
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24972545"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Population-based study on incidence&#44; survival rates&#44; and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Y&#46; Okamoto"
                            1 => "P&#46;L&#46; di Patre"
                            2 => "C&#46; Burkhard"
                            3 => "S&#46; Horstmann"
                            4 => "B&#46; Jourde"
                            5 => "M&#46; Fahey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00401-004-0861-z"
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Neuropathol"
                        "fecha" => "2004"
                        "volumen" => "108"
                        "paginaInicial" => "49"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15118874"
                            "web" => "Medline"
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            ]
            3 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas&#58; data from the SEER program&#44; 1973&#8211;2001"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "E&#46;B&#46; Claus"
                            1 => "P&#46;M&#46; Black"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/cncr.21733"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cancer"
                        "fecha" => "2006"
                        "volumen" => "106"
                        "paginaInicial" => "1358"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16470608"
                            "web" => "Medline"
                          ]
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              ]
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              "identificador" => "bib0195"
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              "referencia" => array:1 [
                0 => array:2 [
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