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 immunoh...
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Published in | Gynecologic oncology Vol. 123; no. 2; pp. 320 - 328 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier Inc
01.11.2011
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Abstract | 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. |
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AbstractList | 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. 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). 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. 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. 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. 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-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. RESULTSE-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. CONCLUSIONSE-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. 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). 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. E-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. E-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. |
Author | Zaino, Richard Ramirez, Nilsa C Weber, Zachary Rittenbach, Jon V Whitney, Charles W Leslie, Kimberly K Brady, William E Singh, Meenakshi Clubwala, Rashna Darcy, Kathleen M Akalin, Ali |
AuthorAffiliation | 7 Milton S. Hershey Medical Center of Pennsylvania State University, Hershey PA 17033 8 Gynecologic Oncology Group Tissue Bank, Biopathology Center, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 5 University of Massachusetts, Worcester, MA 01655 1 State University of New York at Stony Brook, Stony Brook, NY 11794 9 University of Iowa, Iowa City, IA 52246 4 Providence Saint Mary Medical Center, Walla Walla, WA 99362 2 Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York 14263 6 Christiana Gynecologic Oncology, Newark, DE 19713 3 University of Colorado at Denver, Aurora, CO 80202 |
AuthorAffiliation_xml | – name: 1 State University of New York at Stony Brook, Stony Brook, NY 11794 – name: 6 Christiana Gynecologic Oncology, Newark, DE 19713 – name: 7 Milton S. Hershey Medical Center of Pennsylvania State University, Hershey PA 17033 – name: 2 Gynecologic Oncology Group Statistical and Data Center, Roswell Park Cancer Institute, Buffalo, New York 14263 – name: 5 University of Massachusetts, Worcester, MA 01655 – name: 3 University of Colorado at Denver, Aurora, CO 80202 – name: 8 Gynecologic Oncology Group Tissue Bank, Biopathology Center, Research Institute at Nationwide Children's Hospital, Columbus, OH 43205 – name: 9 University of Iowa, Iowa City, IA 52246 – name: 4 Providence Saint Mary Medical Center, Walla Walla, WA 99362 |
Author_xml | – sequence: 1 fullname: Singh, Meenakshi – sequence: 2 fullname: Darcy, Kathleen M – sequence: 3 fullname: Brady, William E – sequence: 4 fullname: Clubwala, Rashna – sequence: 5 fullname: Weber, Zachary – sequence: 6 fullname: Rittenbach, Jon V – sequence: 7 fullname: Akalin, Ali – sequence: 8 fullname: Whitney, Charles W – sequence: 9 fullname: Zaino, Richard – sequence: 10 fullname: Ramirez, Nilsa C – sequence: 11 fullname: Leslie, Kimberly K |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/21813170$$D View this record in MEDLINE/PubMed |
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Keywords | Endometrial cancer p16 Cadherin p120 Catenin p53 |
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Snippet | Abstract Objective We evaluated the clinical relevance of catenins, cadherins and cell cycle regulators in stage IV or recurrent endometrial carcinoma in a... 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... OBJECTIVEWe evaluated the clinical relevance of catenins, cadherins and cell cycle regulators in stage IV or recurrent endometrial carcinoma in a multi-center... |
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SubjectTerms | 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 |
Title | Cadherins, catenins and cell cycle regulators: Impact on survival in a Gynecologic Oncology Group phase II endometrial cancer trial |
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