Study of Molecular Markers in Glioma and Their Association with Clinicopathological Features.

Context: Central nervous system tumors are a major cause of morbidity and mortality worldwide. The most prevalent type of primary brain tumor is glioma. The exploration of significant genetic, epigenetic, and transcriptional abnormalities has not only improved our understanding of glioma pathogenesis but has also revealed that these molecular alterations can serve as useful diagnostic markers for more precise classification and are linked to better treatment response and prognosis. Hence, incorporating molecular markers into routine tumor classification is a major priority in modern glioma diagnostics.

Aim: The aim is to assess the mutation status of isocitrate dehydrogenase (IDH)-1, alpha-thalassemia/mental retardation syndrome X-linked (ATRX), and tumor protein 53 in glioma, and look for their association with various clinicopathological features.

Methodology: A single-center prospective cohort study, where all biopsies of glioma (January 2019 to July 2020) were evaluated, and immunohistochemistry was performed to assess the expression of IDH-1, ATRX, p53, and Ki-67 index. The data were analyzed using IBM SPSS-24 software.

Results: Immunohistochemistry was performed in 123 consecutive cases of glioma. IDH-1 mutation was noted in 54 (43.9%) cases and these patients frequently presented with "seizures" (P = 0.006). The expression was maximum in World Health Organization (WHO) grade 2 tumors (65.4%) (P < 0.001), with the highest frequency in oligodendrogliomas (100% in WHO grade 2 and 3). Furthermore, these tumors showed lower proliferative indices (P = 0.001). ATRX mutation was noted in 59 (48%) and p53 overexpression was noted in 76 (61.8%) cases. These mutations were significantly associated with astrocytic phenotype (P = 0.03).

Conclusions: Molecular characterization of glioma is an important step in modern glioma diagnostics and immunohistochemistry can play an important role. IDH-1 mutation is commonly observed in adults, frontal lobe location, patients presenting with seizures, and WHO grade 2 tumors with the highest frequencies in oligodendrogliomas. ATRX and p53 can be used as surrogate markers for tumors of astrocytic lineage.