title: Epigenetic and immunohistochemical characterization of the Clusterin gene in ovarian tumors.
abstract: OBJECTIVE
  To characterize abnormal epigenetic changes and protein expression of the clusterin gene in a large series of ovarian malignant and borderline tumors.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gynecology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Guofen
authors.initials: G
authors.lastname: Yang
authors.forename: Haihong
authors.initials: H
authors.lastname: Zhang
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.forename: Weipeng
authors.initials: W
authors.lastname: He
authors.forename: Charles M
authors.initials: CM
authors.lastname: Quick
authors.forename: Dan
authors.initials: D
authors.lastname: Xie
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Smoller
authors.forename: Chun-Yang
authors.initials: CY
authors.lastname: Fan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077216:Carcinoma, Ovarian Epithelial; D051152:Clusterin / Q000032:analysis* / Q000235:genetics*; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008643:Mesentery / Q000473:pathology; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry / Q000235:genetics; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000235:genetics*; D010053:Ovary / Q000737:chemistry; D011401:Promoter Regions, Genetic / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: C495242:CLU protein, human; D051152:Clusterin