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

ObjectiveWe 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).MethodsTissue 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-cadherinE, N-cadherinE, alpha-cateninE, beta-cateninE, gamma-cateninE, p120-cateninE and Ki-67E; as negative, below median or above median for p16E, p27E and CD44S; or as negative or positive for p53E, Ki-67S and APCS (adenomatous polyposis coli). End points included response and survival.ResultsE-cadherinE, p16E, and p53E varied by race (p = 0.003, p = 0.024, p = 0.002,) and N-cadherinE, Ki-67E, p16E and p27E by tumor type (p = 0.015, p = 0.011, p = 0.005, p = 0.021). Correlations were observed among E-cadherinE with p120E (r = 0.66), p53E (r = − 0.32), alpha-cateninE (r = 0.52), beta-cateninE (r = 0.58), and gamma-cateninE (r = 0.58). High E-cadherinE (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 p16E 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 p53E was associated with worse survival in unadjusted (HR = 2.31, 95% CI = 1.16–4.60) but not adjusted models.ConclusionsE-cadherinE and p16E 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.

► High E-cadherin expression is associated with better survival.
► High p16 expression is associated with worse survival.
► E-cadherin and p16: independent prognostic factors in advanced endometrial cancers.