Decreased expression of RIZ1 and its clinicopathological significance in epithelial ovarian carcinoma: Correlation with epigenetic inactivation by aberrant DNA methylation

Abstract

The retinoblastoma protein-interacting zinc finger gene (RIZ1) is considered a tumor suppressor gene. The purpose of the present study was to examine the expression of RIZ1 and evaluate its clinicopathological significance in ovarian carcinoma. Immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-PCR) was performed for RIZ1 and its clinicopathological significance was examined. DNA methylation status of RIZ1 was also studied. All (6/6) of the normal, 5/9 of benign, and 4/9 of borderline tissues were positive for RIZ1 protein. In ovarian cancer tissues 32.9% (54/164) were positive for RIZ1. Decreased expression of RIZ1 was significantly correlated with histological subtypes (P < 0.0001), high tumor grade (P = 0.0153) and advanced clinical stage (P = 0.0345), and high Ki67 index (P = 0.0117) but was not associated with the overall prognoses of the patients (P = 0.519). The presence of methylated band was detected in 2/9 cell lines, and 5/69 ovarian cancer tissues. Median values of relative RIZ1 expression in cell lines with methylation were significantly lower than those without methylation (P = 0.0404), and treatment of 5-aza-2'deoxycitidine resulted in demethylation and re-expression of RIZ1. Reduced expression of RIZ1 may play an important role in the pathogenesis and/or development of epithelial ovarian carcinoma, and is considered to be caused in part by aberrant DNA methylation.