Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer

J Ovarian Res. 2014 Feb 6:7:16. doi: 10.1186/1757-2215-7-16.

Abstract

Background: β-catenin is the key protein in the WNT signalling pathway and it forms adherent junctions together with E-cadherin. In ovarian carcinoma, abnormal expression of β-catenin, E-cadherin and WNT-1 was observed, but their prognostic and predictive role is unclear. The aim of this study was to clarify the prognostic and predictive role of E-cadherin, β-catenin and WNT-1 in advanced epithelial ovarian carcinoma (AEOC).

Methods: The expression of E-cadherin, β-catenin and WNT-1 was determined by immunohistochemistry in AEOC. The correlation between expression of these proteins and progression-free survival (PFS) and overall survival (OS) was evaluated. Statistical analyses included Kaplan-Meier estimation, log-rank test, Spearman correlation and Cox proportional-hazards model.

Results: In ovarian cancer, intense expression of E-cadherin, β-catenin and WNT-1 was found. In multivariate analysis, strong membrane β-catenin expression was an independent unfavourable predictor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028), while in univariate analysis, strong membrane β-catenin expression was a prognostic factor for OS in patients with AOC (p = 0.039). In multivariate analysis, only resistance to first-line chemotherapy was an adverse independent prognostic factor for OS (HR 16.84; 95% CI 5.07-55.98; p < 0.0001). Additionally, strong membranous β-catenin expression was associated with resistance to platinum-based chemotherapy (p = 0.027).

Conclusions: These findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antigens, CD
  • Biopsy
  • Cadherins / analysis*
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Glandular and Epithelial / chemistry*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / chemistry*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Proportional Hazards Models
  • Risk Factors
  • Time Factors
  • Wnt Signaling Pathway*
  • Wnt1 Protein / analysis*
  • beta Catenin / analysis*

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • WNT1 protein, human
  • Wnt1 Protein
  • beta Catenin