title: 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.
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Japan. jakahira-tohoku@umin.ac.jp
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Akahira
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Suzuki
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ikumi
authors.initials: I
authors.lastname: Miura
authors.forename: Noriko
authors.initials: N
authors.lastname: Kamogawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ito
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D005260:Female; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human