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EZH2 expression in gliomas: Correlation with CDKN2A gene deletion/ p16 loss and MIB ‐1 proliferation index
Author(s) -
Purkait Suvendu,
Sharma Vikas,
Jha Prerana,
Sharma Mehar Chand,
Suri Vaishali,
Suri Ashish,
Sharma BS,
Sarkar Chitra
Publication year - 2015
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12201
Subject(s) - cdkn2a , ezh2 , cancer research , immunohistochemistry , gene expression , medicine , biology , pathology , gene , cancer , genetics
Enhancer of zeste homolog 2 ( EZH2 ) mediated down‐regulation of CDKN2A /p16 has been observed in cell lines as well as in a few carcinomas. However, there is no study correlating EZH2 expression with CDKN2A /p16 status in gliomas. Hence, the present study was conducted to evaluate EZH2 expression in astrocytic and oligodendroglial tumors and correlate with CDKN2A /p16 status as well as MIB ‐1 labeling index ( LI ). Gliomas of all grades ( n = 118) were studied using immunohistochemistry to assess EZH2 , p16 and MIB ‐1 LI and fluorescence in situ hybrization to evaluate CDKN2A gene status. EZH2 expression and CDKN2A homozygous deletion ( HD ) were both significantly more frequent in high‐grade gliomas ( HGG ). Further, strong EZH2 expression ( LI ≥ 25%) was significantly more common in HGGs without CDKN2A HD (48.7%; 19/39) as compared to cases with deletion (15.8%; 3/19). Loss of p16 expression was noted in 100% and 51.3% of CDKN2A deleted and non‐deleted tumors, respectively. Notably, 80% (16/20) of the CDKN2A non‐deleted HGGs with p16 loss had strong EZH2 expression, in contrast to only 15.8% (3/19) in the deleted group. Loss of p16 expression significantly correlated with MIB ‐1 LI , irrespective of EZH2 status. Thus, this study shows that EZH2 expression correlates with tumor grade in both astrocytic and oligodendroglial tumors and hence can be used as a diagnostic marker to differentiate between low and HGGs . Further, this is the first report demonstrating an inverse correlation of strong EZH2 expression with CDKN2A HD in HGGs . Loss of p16 protein expression is mostly attributable to CDKN2A HD and correlates significantly with MIB ‐1 LI . Notably, our study for the first time suggests a possible epigenetic mechanism of p16 loss in CDKN2A non‐deleted HGGs mediated by strong EZH2 expression. A hypothetical model for control of proliferative activity in low versus HGGs is therefore proposed.