Significance of E-Cadherin and p16 Advanced Endometrial Cancer: A Gynecologic Oncology Group Phase II Study
M Singh, KM Darcy, WE Brady, Z Weber, A Akalin, CW Whitney, R Zaino, N Ramirez, KK Leslie. SUNY at Stony Brook & SBUMC, Stony Brook, NY; Gynecologic Oncology Group, Buffalo; University of Colorado Denver, Aurora; University of Massachusetts, Worcester; Christiana Gynecology Group, Newark, DE; Hershey Medical Center, Hershey; Nationwide Children's Hospital, Columbus, OH; University of Iowa, Iowa City
Background: Biomarkers in advanced endometrial cancers have the potential for guiding treatment and improving patient survival. Our aim was to evaluate the cadherin-catenin complex biomarkers in advanced endometrial carcinoma patients treated with tamoxifen and medroxyprogesterone acetate (T+M) in a multi-center phase II trial (GOG protocol # 119).
Design: Tissue microarrays with multiple replicate cores of endometrial carcinoma tissue from 42 patients with stage IV or recurrent tumor were evaluated immunohistochemically for expression of the proteins of the cadherin-catenin pathway, proliferation markers, cell cycle inhibitors & p53. Expression in epithelium (E) was categorized into tertiles (T1, T2, T3) for E-cadherin, N-cadherin, alpha-catenin, beta-catenin, gamma-catenin, p120-catenin and Ki-67; as negative, below median or above median for p16 and p27; and as negative or positive for p53. Expression in stroma (S) was categorized as negative or positive for Ki-67. Clinicopathologic correlations were analyzed.
Results: Relationships were observed between race and E-cadherinE (p=0.003) and p16E (p=0.024); histologic type of cancer and N-cadherinE (p=0.015), Ki-67E (p=0.011), p16E (p=0.005) and p27E (p=0.021); and between patient age and p16E (p=0.036). E-cadherinE expression (T2 or T3 versus T1) was associated with a reduced risk of progression (p=0.008 or p=0.006, respectively) or death (p<0.001 or p<0.001, respectively) and was an independent prognostic factor for better progression free survival (PFS) (p=0.025 or p=0.112, respectively) and overall survival (OS) (p=0.004 or p=0.01, respectively). In addition, expression above the mean versus no expression of p16E was associated with an increased risk of death (p<0.001) and was an independent prognostic factor for worse OS (p=0.018) while positive versus no expression of p53E was associated with worse OS (p=0.018).
Conclusions: E-cadherinE and p16E appear to be clinically relevant and of prognostic value in stage IV or recurrent endometrial cancer treated with T+M.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 131, Wednesday Morning