DIPG-33. P16 IMMUNOHISTOCHEMICAL EXPRESSION AS A SURROGATE ASSESSMENT OF CDKN2A ALTERATION IN GLIOMAS LEADING TO PROGNOSTIC SIGNIFICANCES

Abstract

Abstract CDKN2A is a tumor suppressor gene encoding for p16 protein. Its homozygous deletion is a central prognostic factor for numerous brain cancers. This deletion can be detected by several techniques. Up to now, immunohistochemistry (IHC) using p16 antibody is not recommended as a surrogate test. This study aimed to evaluate to what extent IHC levels of p16 expression may provide information about CDKN2A homozygous deletion. A retrospective study was conducted in 173 gliomas comprising 50 circumscribed low-grade MAPK-altered gliomas, 18 pediatric diffuse high-grade gliomas (HGG), and 105 adult-type diffuse gliomas of all grade, using p16 IHC and CDKN2A fluorescent in situ hybridization. Survival analyses were performed to assess their prognostic impact. Three patterns of p16 expression were observed: absence of expression, focal expression and overexpression. The prognostic impact of p16 overexpression was dependent on the tumor drivers. Indeed, it was associated to a better prognosis in MAPK-induced tumors, but to a worse survival in IDH-wild-type glioblastomas. CDKN2A homozygous deletion present in all type of high grade pediatric or adult gliomas was significantly linked to a worse outcome in the entire population. Regarding specifically to H3K27-altered gliomas, no significant prognostic impact was observed, probably related to the small size of our population. Nevertheless, this p16 lost expression was rarely reported in this pediatric population. The lost expression was observed in 7/9 H3K27M-mutants and in 6/8 wild-type cases. Its implication should be considered more largely and is probably opening the path for therapies targeting the p16 pathway in this population. Regarding the IHC technique itself, beyond the association between absence of p16 protein expression and the CDKN2A loss (p<0.001), this technique seems to have a strong sensitivity and a high negative predictive value. These data suggest that p16 IHC might be a pertinent test to detect cases harboring CDKN2A homozygous deletion.