위샘암종에서 EZH2, p16및 Ki-67 발현의 의의

Abstract

Background: At the molecular level, gastric tumors arise from multiple genetic and epigenetic alterations that involve oncogenes, tumor suppressor genes, cell cycle regulators, cell adhesion molecules and DNA repair genes. The enhancer of zeste homolog 2 (EZH2), a member of the polycomb group of protein, plays an important role in cell proliferation and cell cycle regulation. EZH2 was overexpressed in aggressive forms of prostate, breast, bladder and endometrial cancers. p16 gene is implicated in pathogenesis of many human tumors and even in regulation of normal cellular growth, together with tyrosine kinases and tumor transforming growth factors. This study aimed to evaluate the clinicopathologic significance of the expression of three proteins, tissue development and EZH2 differentiation , crucial to cell-cycle p16 control and Ki-67 in patients with gastric adenocarcinoma. Methods: The expression patterns were examined by immunohistochemistry in 115 patients. The results were compared with both clinicopathologic factors (age, sex, Lauren classification type, histologic grade, tumor size, pT stage, lymph node metastasis, and stage) and the overall survival. Results: The expression of EZH2, p16 and Ki-67 was not correlated with any clinicopathologic factors. High expression of EZH2 was significantly correlated with score of Ki-67 expression in gastric adenocarcinoma. Multivariate analysis showed that tumor location, histologic grade, pT, pN and loss of p16 expression had a significant correlation with survival. Conclusion: These results demonstrated that correlation between loss of p16 expression, each tumor location, histologic grade, pT or survival was found. Therefore, p16 expression may be an additional prognostic marker, and provides useful information for survival in gastric cancer patients. The siginificance of relationship between EZH2 and Ki-67 expression will be needed to determine by additional research in future.