TY - JOUR
T1 - Cadherins, catenins and cell cycle regulators
T2 - Impact on survival in a Gynecologic Oncology Group phase II endometrial cancer trial
AU - Singh, Meenakshi
AU - Darcy, Kathleen M.
AU - Brady, William E.
AU - Clubwala, Rashna
AU - Weber, Zachary
AU - Rittenbach, Jon V.
AU - Akalin, Ali
AU - Whitney, Charles W.
AU - Zaino, Richard
AU - Ramirez, Nilsa C.
AU - Leslie, Kimberly K.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Cadherin
KW - Catenin
KW - Endometrial cancer
KW - p120
KW - p16
KW - p53
UR - http://www.scopus.com/inward/record.url?scp=80054741190&partnerID=8YFLogxK
U2 - 10.1016/j.ygyno.2011.07.005
DO - 10.1016/j.ygyno.2011.07.005
M3 - Article
C2 - 21813170
AN - SCOPUS:80054741190
SN - 0090-8258
VL - 123
SP - 320
EP - 328
JO - Gynecologic Oncology
JF - Gynecologic Oncology
IS - 2
ER -