title: Claudin upregulation in ovarian carcinoma effusions is associated with poor survival.
abstract: Claudins are tight junction proteins that are highly expressed in ovarian carcinoma (OC). The objective of this study was to analyze the anatomic site-related expression and clinical role of claudins in OC. Effusions (n = 218), corresponding primary tumors (n = 81), and solid metastases (n = 164) (total = 463 tumors) were immunostained for claudin-1, claudin-3, claudin-4, and claudin-7. Results were analyzed for association with anatomic site, clinicopathologic parameters, and survival. All 4 claudins were expressed in >85% of tumors at all anatomic sites. However, staining extent of all except claudin-4 was significantly higher in effusions compared with both primary carcinomas and solid metastases (P < .001). In univariate survival analysis of the entire cohort, higher claudin-3 (P = .038) and claudin-7 (P = .035) expression in effusions correlated with shorter overall survival (OS), with similar results for claudin-7 in analysis of progression-free survival (P = .026). In separate analysis for patients with prechemotherapy effusions, higher claudin-7 expression correlated with shorter OS (P = .045). For patients with postchemotherapy effusions, higher claudin-1 (P = .018) and claudin-3 (P = .009) expression correlated with shorter OS. In multivariate survival analysis of the entire cohort, claudin-7 expression was an independent predictor of poor progression-free survival (P = .017). Claudin-3 independently predicted poor OS for patients with postchemotherapy effusions (P = .012). With the exception of claudin-4, claudins are upregulated in OC effusions compared with solid tumors, in agreement with our previous data for cadherins and integrins in this cancer type, suggesting a prosurvival role for these surface molecules. Claudin-3 and claudin-7 expression in effusions independently predicts poor survival in OC.
authors.affiliation: Pathology Clinic, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, N-0310 Oslo, Norway.
authors.forename: Lilach
authors.initials: L
authors.lastname: Kleinberg
authors.forename: Arild
authors.initials: A
authors.lastname: Holth
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope
authors.forename: Reuven
authors.initials: R
authors.lastname: Reich
authors.forename: Ben
authors.initials: B
authors.lastname: Davidson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D062445:Claudin-1; D062465:Claudin-3; D057167:Claudins; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016019:Survival Analysis; D015854:Up-Regulation
chemical_list: C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C473255:CLDN7 protein, human; D062445:Claudin-1; D062465:Claudin-3; D057167:Claudins; D008565:Membrane Proteins