Cadherins, catenins and cell cycle regulators: Impact on survival in a Gynecologic Oncology Group phase II endometrial cancer trial

Abstract

Objective: We evaluated the clinical relevance of catenins, cadherins and cell cycle regulators in stage IV or recurrent endometrial carcinoma in a multi-center phase II trial (GOG protocol #119). Methods: Tissue microarrays of metastatic or recurrent (n = 42) tumor were developed and immunohistochemistry was performed. Average expression (percent staining x intensity) was assessed in tumor epithelium ( E) and stroma ( S) and categorized into tertiles (T1, T2, T3) for E-cadherin E, N-cadherin E, alpha-catenin E, beta-catenin E, gamma-catenin E, p120-catenin E and Ki-67 E; as negative, below median or above median for p16 E, p27 E and CD44 S; or as negative or positive for p53 E, Ki-67 S and APC S (adenomatous polyposis coli). End points included response and survival. Results: E-cadherin E, p16 E, and p53 E varied by race (p = 0.003, p = 0.024, p = 0.002,) and N-cadherin E, Ki-67 E, p16 E and p27 E by tumor type (p = 0.015, p = 0.011, p = 0.005, p = 0.021). Correlations were observed among E-cadherin E with p120 E (r = 0.66), p53 E (r = - 0.32), alpha-catenin E (r = 0.52), beta-catenin E (r = 0.58), and gamma-catenin E (r = 0.58). High E-cadherin E (T2 or T3) versus low (T1) expression was associated with better survival in unadjusted (hazard ratio [HR] = 0.14, 95% confidence interval [CI] = 0.06-0.37 or HR = 0.17, 95% CI = 0.07-0.42) and adjusted models (HR = 0.18, 95% CI = 0.05-0.59 or HR = 0.22, 95% CI = 0.07-0.70). High p16 E versus negative expression was associated with worse survival in unadjusted (HR = 3.87, 95% CI = 1.74-8.61) and adjusted (HR = 4.18, 95% CI = 1.28-13.6) models. Positive versus negative expression of p53 E was associated with worse survival in unadjusted (HR = 2.31, 95% CI = 1.16-4.60) but not adjusted models. Conclusions: E-cadherin E and p16 E appear to be clinically relevant, independent prognostic factors in stage IV or recurrent endometrial cancers treated with Tamoxifen and Medroxyprogesterone acetate, and merit further study. © 2011 Elsevier Inc. All rights reserved.