RESUMO
La Clasificación de Tumores del Sistema Nervioso Central de la OMS 2016 incorpora biomarcadores moleculares junto a las características histológicas clásicas, en un diagnóstico integrado, con el fin de definir distintas entidades de gliomas con la mayor precisión posible. Los estudios de perfiles moleculares en el genoma han revelado las alteraciones genéticas características y los perfiles epigenéticos asociados con diferentes tipos de gliomas. Estas características moleculares pueden usarse para refinar la clasificación del glioma, mejorar la predicción de los resultados obtenidos con los tratamientos actuales y futuros en los pacientes, y como guía de un tratamiento personalizado. Asimismo, tener una aproximación pronóstica en cada paciente. Este cambio de paradigma ha modificado la forma en que se diagnostica el glioma y sus implicancias en la práctica diaria en la indicación de los diferentes tratamientos al paciente. Aquí, sintéticamente, revisamos y destacamos los biomarcadores moleculares clínicamente relevantes. Intentamos dejar plasmado cómo los avances en la genética molecular de los gliomas pueden promover y allanar el camino hacia la medicina de precisión en neurooncología.
The Classification of Tumors of the Central Nervous System of the WHO 2016 incorporates molecular biomarkers together with the classical histological characteristics, in an integrated diagnosis, in order to define different glioma entities with the highest possible accuracy. Studies of molecular profiles in the genome have revealed characteristic genetic alterations and epigenetic profiles associated with different types of gliomas. These molecular characteristics can be used to refine the classification of gliomas, improve the prediction of the results obtained with current and future treatments in patients and as a guide for a personalized treatment. Also, have a prognostic approach in each patient. This paradigm shift has modified the way glioma is diagnosed and its implications in daily practice in the indication of different treatments to the patient. Here, synthetically, we review and highlight clinically relevant molecular biomarkers. We try to capture how advances in the molecular genetics of gliomas can promote and pave the way to precision medicine in neuro-oncology.
Assuntos
Humanos , Glioma , Biomarcadores , Sistema Nervoso Central , Biologia Molecular , NeoplasiasRESUMO
BACKGROUND AND OBJECTIVES: 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. MATERIALS AND METHODS: Retrospective review of glial tumours (oligodendrogliomas and astrocytomas) treated in our centre between January 2012 and June 2016 in which a review of diagnosis was performed when molecular studies were added. Statistical analysis included evaluation of variables of epidemiology, morphology and molecular data (mainly IDH mutation and 1p19q codeletion), diagnostic changes after new classification was considered, and clinical impact in cases of diagnostic reclassification. RESULTS: From a total of 147 glial tumours reviewed in our centre, molecular diagnosis was obtained in 74 cases (50.3%). Initial diagnosis changed in 23 cases (31%), and 20 (87%) of them had a prior histological diagnosis of oligodendroglioma (69.6% grade ii and 17.4% grade iii). Only 3 of these 23 cases diagnosis changed from astrocytoma to oligodendroglioma. Among reclassified tumours, there was a common molecular pattern, as findings showed mutant IDH in 16 cases (69.6%) and no codeletion in 20 cases (87%). According to the cell of origin, of the whole group of 27 oligodendrogliomas in our series (reclassified and non-reclassifed), 20 cases (74%) became astrocytomas, despite typical oligodendroglial morphology, due to absence of 1p19q codeletion. There was a trend for diagnosis reclassification in younger patients (<40 years), P=.065, mainly in those with a prior diagnosis of oligodendroglioma, with no statistical differences based on gender or clinical data. Besides, reclassification was more common among tumours with mutant IDH (69.6%), P=.003, than those with wild type IDH. In terms of survival, despite receiving different treatments, no significant changes were detected between reclassified and non-reclassified tumours after a mean follow-up of 16 months, partly related to lower grade of these lesions. CONCLUSIONS: Within the spectrum of the glial tumours treated in our institution, this new classification including molecular genetics over morphological data has provided marked diagnostic changes. These changes appear mainly in tumours previously diagnosed as oligodendrogliomas and in younger patients, with molecular patterns of mutant IDH and 1p19q codeletion. Although diagnosis reclassification may affect clinic, prognosis or therapeutic management of these tumours, deeper and prospective studies on these specific aspects are needed.
