title: Loss of ARID1A expression is related to shorter progression-free survival and chemoresistance in ovarian clear cell carcinoma.
abstract: Recently, the ARID1A gene has been identified as a novel tumor suppressor in ovarian clear cell carcinoma. The prognostic significance of the loss of ARID1A expression is not known. The current study was designed to evaluate whether ARID1A was a prognostic factor for progression, survival, and chemoresistance in ovarian clear cell carcinoma. A total of 60 patients, who were surgically treated for primary ovarian clear cell adenocarcinoma, were enrolled. Surgical specimens were examined for ARID1A protein expression by immunohistochemistry. The correlations between the loss of ARID1A expression and clinicopathological characteristics, prognosis, and chemosensitivity were investigated. Loss of ARID1A expression was identified in 9 (15.0%) of 60 ovarian clear cell carcinoma samples. Loss of ARID1A staining intensity (0+) was more frequently found in cells of clear cell carcinomas than in high-grade serous carcinomas (P<0.01). Loss of ARID1A expression was significantly correlated with advanced FIGO stage and high CA125 levels (P=0.02, 0.01). There were no significant correlations between loss of ARID1A expression and patient age, status of residual tumor, Ki-67 labeling index, or the status of endometriosis. Loss of ARID1A correlated with shorter progression-free survival of patients with clear cell carcinomas treated with platinum-based chemotherapy (P<0.01). Loss of ARID1A expression tended to correlate with shorter overall survival in patients with ovarian clear cell carcinomas treated with platinum-based chemotherapy. When data were stratified for the multivariate analysis, only the loss of ARID1A expression remained a significant (P=0.03) predictor of reduced progression-free survival. Of the 60 patients with ovarian clear cell carcinomas, 14 patients had measurable residual tumor after primary cytoreductive surgery. Tumors with loss of ARID1A expression were more likely to be chemoresistant than tumors with positive ARID1A expression (100.0 vs 40.0%, P=0.04). This study demonstrates that loss of ARID1A in ovarian clear cell carcinoma is a negative prognostic factor in patients treated with platinum-based chemotherapy. Measurement of ARID1A expression may be a method to predict resistance to platinum-based chemotherapy in patients with ovarian clear cell carcinoma.
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Katagiri
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.forename: Mohammed Tanjimur
authors.initials: MT
authors.lastname: Rahman
authors.forename: Munmun
authors.initials: M
authors.lastname: Rahman
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katagiri
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakayama
authors.forename: Masako
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Tomoka
authors.initials: T
authors.lastname: Ishibashi
authors.forename: Kouji
authors.initials: K
authors.lastname: Iida
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Otsuki
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakayama
authors.forename: Kohji
authors.initials: K
authors.lastname: Miyazaki
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D000970:Antineoplastic Agents / Q000627:therapeutic use; D004268:DNA-Binding Proteins; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017671:Platinum Compounds / Q000627:therapeutic use; D011379:Prognosis; D016016:Proportional Hazards Models; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D017671:Platinum Compounds; D014157:Transcription Factors