Epigenetic and immunohistochemical characterization of the Clusterin gene in ovarian tumors

Abstract

To characterize abnormal epigenetic changes and protein expression of the clusterin gene in a large series of ovarian malignant and borderline tumors. Protein expression and promoter methylation of clusterin gene in 181 primary ovarian epithelial cancer, 40 borderline ovarian tumors, 54 ovarian cancer mesenteric metastasis, and 10 normal ovarian samples were analyzed by immunohistochemical staining and methylation-specific PCR. Overexpression of clusterin protein was frequently seen in various ovarian epithelial tumors, being detected in 102 of 181 (56%) primary ovarian epithelial cancers, 21 of 37 (57%) borderline ovarian tumors. Surprisingly, clusterin protein expression was significantly reduced in mesenteric metastasis (20 of 54; 37% cases), as compared to primary ovarian carcinoma (p=0.01). Overexpression of clusterin protein was significantly correlated with high-grade histology (p=0.002) and high FIGO stages (p=0.05). Clusterin promoter hypermethylation was detected in 24 of 181 (13%) primary ovarian epithelial cancer, 8 of 54 (14%) mesenteric metastasis, and 10 of 37 (27%) borderline ovarian tumors. Overall, clusterin promoter hypermethylation was significantly correlated with decreased protein expression in these samples (p<0.001). Increased clusterin expression is correlated with more aggressive biologic behavior in ovarian cancer. Promoter methylation of the clusterin gene can be readily detected, though at low frequencies, in ovarian epithelial tumors and is significantly associated with decreased protein expression of the gene.