P17.71 * ROLE OF ATRX AND TERT EXPRESSION AS DIAGNOSTIC AND PROGNOSTIC FACTORS ON ANAPLASTIC GLIOMAS

Abstract

Molecular and histological classification of anaplastic gliomas have been recently refined by the elucidation of the role of mutations in alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene and in telomerase reverse transcriptase (TERT) promoter. Loss of ATRX expression and the acquisition of alternative lengthening of telomeres (ALT) phenotype is peculiar of a subtype of astrocytic tumours with p53 and IDH1 mutations and better prognosis, while TERT overexpression, due to its promoter's mutations, is strongly associated to oligodendroglial tumours and 1p/19q codeletion, without a significant correlation with survival. Based on these findings, the aim of our study was to better clarify the role of ATRX and TERT expression in the histological classification of anaplastic gliomas, as diagnostic and prognostic markers of survival and relapse. We performed immunohistochemical and molecular analysis of ATRX and TERT expression on 60 grade III gliomas (astrocytomas, oligoastrocytomas and oligodendrogliomas) and the respective recurrences when they were available. Nuclear accumulation of p53, IDH1 status and LOH of chromosomes 1p, 19q, 9p, 17p and 10q were also evaluated. Our results showed a loss of ATRX expression in 60% of anaplastic oligoastrocytomas and 40% of anaplastic astrocytomas, while ATRX was wild-type in oligodendroglial tumours. We then found a strong positive correlation between loss of ATRX expression and p53 nuclear accumulation, while its strong expression was present mostly in tumours with 1p/19q codeletion. Finally, ATRX loss was correlated with a better prognosis both in anaplastic oligoastrocytomas and in anaplastic astrocytomas according to literature. Regarding TERT expression, we did not find a strictly correlation with 1p/19p codeletion and the oligodendroglial histological pattern, but, surprisingly, we found a possible role in relapse of anaplastic gliomas. In our series, tumours with high TERT expression tend to recur within 25 months, while anaplastic gliomas with low o null expression of TERT tend to recur within 60 months. In conclusion, these set of data could allow us in the future to better classify anaplastic gliomas and their tendency to recur adding immunohistochemistry for ATRX and TERT to other molecular markers in routine diagnostic procedures, and to define new molecular profiles for their therapy.