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

• Published in: Gynecologic oncology Vol. 123; no. 2; pp. 320 - 328
• Main Authors: Singh, Meenakshi, Darcy, Kathleen M, Brady, William E, Clubwala, Rashna, Weber, Zachary, Rittenbach, Jon V, Akalin, Ali, Whitney, Charles W, Zaino, Richard, Ramirez, Nilsa C, Leslie, Kimberly K
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2011
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Cadherin; Cadherins - analysis; Catenin; Catenins - analysis; Cell Cycle Proteins - analysis; Endometrial cancer; Endometrial Neoplasms - chemistry; Endometrial Neoplasms - mortality; Endometrial Neoplasms - pathology; Female; Guanine Nucleotide Exchange Factors - analysis; Hematology, Oncology and Palliative Medicine; Humans; Immunohistochemistry; Middle Aged; Neoplasm Staging; Nuclear Proteins - analysis; Obstetrics and Gynecology; p120; p16; p53; Prognosis; Endometrial cancer; p16; Cadherin; p120; Catenin; p53
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2011.07.005

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-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. 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.