Epigenetic Inactivation of Clusterin Gene May Predict for Mesenteric Metastasis of Primary Ovarian Cancer
CM Quick, HH Zhang, GF Yang, CY Fan. University of Arkansas for Medical Sciences, Little Rock, AR; John L. McClellan Memorial Veterans Hospital and UAMS, Little Rock, AR; The First Affiliated Hospital, Sun Yat-Sen Univ Med Sciences, Guangzhou, China
Background: Clusterin, a multifunctional glycoprotein, is ubiquitously produced in mammalian tissues. Clusterin has been shown to play significant roles in many aspects of human tumor biology, such as cell-cell adhesion, cell proliferation, apoptosis, chemoresistance and angiogenesis. While clusterin is shown to be overexpressed in many types of human malignant tumors, its exact roles in the biologic behavior in ovarian epithelial cancer have not been fully investigated.
Design: Immunohistochemical (IHC) staining for clusterin was performed on a Tissue Microarray (TMA) containing 50 primary ovarian epithelial cancer (39 serous; 11 mucinous) and 50 matched mesenteric metastasis. Methylation-specific PCR for clusterin gene promoter was performed on all 100 tumors to determine whether clusterin protein expression is affected by promoter hypermethylation.
Results: High levels of clusterin protein were seen in 32 of 50 (64%) primary ovarian epithelial carcinoma and in 17 of 50 (34%) matched mesenteric metastasis. Decreased clusterin protein expression was significantly correlated with mesenteric metastasis (p = 0.03). Clusterin promoter hypermethylation was seen in 3/50 (6%) primary cancer and in 8/50 (16%) metastatic lesions. Among 8 metastatic lesions that displayed clusterin promoter hypermethylation, 7 were seen in metastatic lesions but not in their corresponding primary tumors. Among these 7 cases, 5 demonstrated significant reduction of clusterin protein expression in metastatic lesions as compared to that in their corresponding primary tumors.
Conclusions: Decreased clusterin protein expression is significantly correlated with mesenteric metastasis of ovarian cancer and promoter hypermethylation of the clusterin gene appears to play important roles in silencing the clusterin gene expression in these metastatic lesions.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 166, Wednesday Afternoon