Immunohistochemical analysis of polycomb group protein expression in advanced gastric cancer.

Abstract

The polycomb group proteins have recently captured the attention of cancer biologists. enhancer of zeste homologue 2 (EZH2) and B lymphoma Mo-MLV insertion region 1 homolog (BMI-1) are the best-characterized polycomb group proteins; their deregulation contributes to the development of many malignancies including gastric cancers. H3 trimethylation at lysine 27 and DNA methylase DNA methyltransferase 3B proteins are associated with the recruitment of polycomb group proteins. Overexpression of polycomb group proteins is associated with poor prognoses in some types of cancers but with favorable prognoses in others. In the present study, we investigated the expression of the polycomb group proteins EZH2 and BMI-1 and the associated proteins H3 trimethylation at lysine 27 and DNA methyltransferase 3B in advanced gastric cancers. Based on immunohistochemical detection, we evaluated the clinical relevance of these proteins in 178 cases of advanced gastric cancers that were managed with radical surgery and adjuvant systemic chemotherapy. BMI-1, enhancer of zeste homologue 2, H3 trimethylation at lysine 27, and DNA methyltransferase 3B proteins were overexpressed in the nuclei of gastric carcinoma compared with adjacent nonneoplastic gastric parenchyma. The high-level expression of BMI-1, enhancer of zeste homologue 2, H3 trimethylation at lysine 27, and DNA methyltransferase 3B proteins were frequently noted in advanced gastric cancer tissues (70.8%, 92.1%, 58.4%, and 64.6% of cases, respectively) and well intercorrelated in expression (P < .05). The expression level of BMI-1, enhancer of zeste homologue 2, and DNA methyltransferase 3B showed correlation with sex, gross type, and histologic type of the tumor among clinicopathologic variables. In terms of patient survival, low-level expression of enhancer of zeste homologue 2 was associated with cancer-related death (P = .018) and shorter overall survival (P = .005). Low-level expression of enhancer of zeste homologue 2 may represent a negative prognostic marker (P = .005) and indicate high risk in patients with advanced gastric cancer after surgery and adjuvant chemotherapy.