Alterações moleculares em gliomas: perfil imuno-histoquímico, biomarcadores tumorais e potenciais alvos terapêuticos

Abstract

Gliomas are the most common primary malignant tumours of the central nervous system, presenting several molecular alterations that account for the mechanisms of gliomagenesis. This study is a retrospective cross-sectional analysis of 241 adult patients with cerebral gliomas, presented between 2013 and 2023 at a reference hospital in Brazil. The research aimed to evaluate the biomarkers EGFR, Pan-TRK, IDH1, PD-L1, H3K27M, ATRX, P53, HER2, and Ki-67 in patients with specific gliomas and their correlations with epidemiological, clinical, radiological, histopathological aspects, overall and progression-free survival, as well as the relationship between these gliomagenic pathways, highlighting their therapeutic potential. The selected cases underwent tissue microarray (TMA) and immunohistochemical study. Immunological detection of H3K27M, Pan-TRK, ATRX mutations, IDH1, and the non-mutated p53 pattern confirmed them as good prognostic markers. The H3K27M biomarker exhibited lower tumour grade, predominance of low-grade morphological characteristics, IDH1 mutation, and a non-mutated p53 pattern, in addition to better survival curves. Pan-TRK immunodetection was related to less infiltration of structures, IDH1 mutation, absence of PD-L1 immunodetection, lower Ki-67 index, and a non-mutated p53 pattern, as well as better survival curves and a reduced risk of tumour recurrence. The ATRX mutation is associated with the absence of micro vascularization. IDH1 showed a relationship with the population up to 50 years old, immunodetection of H3K27M, Pan-TRK, and PD-L1, in addition to lower Ki-67 indices, absence of EGFR immunodetection, and better survival curves. The non-mutated p53 pattern exhibits a lower need for adjuvant therapy. The biomarkers EGFR, PD-L1, and the mutated p53 pattern were confirmed as markers of worse prognosis. PD-L1 immunodetection was associated with higher mitotic activity and worse survival curves. EGFR positivity showed higher detection in GBMs and a relationship with wild-type IDH tumours. The mutated p53 pattern was associated with higher detection in patients over 50 years of age. The immunoreaction for the HER2 marker was excluded in only one patient, with no statistically significant results. Molecular characterization in routine tumour management is gaining increasing importance, providing therapeutic guidance and prognosis.