title: 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 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.
authors.affiliation: State University of New York at Stony Brook, Stony Brook, NY 11794, USA. meenakshi.singh@stonybrook.edu
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Singh
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Darcy
authors.forename: William E
authors.initials: WE
authors.lastname: Brady
authors.forename: Rashna
authors.initials: R
authors.lastname: Clubwala
authors.forename: Zachary
authors.initials: Z
authors.lastname: Weber
authors.forename: Jon V
authors.initials: JV
authors.lastname: Rittenbach
authors.forename: Ali
authors.initials: A
authors.lastname: Akalin
authors.forename: Charles W
authors.initials: CW
authors.lastname: Whitney
authors.forename: Richard
authors.initials: R
authors.lastname: Zaino
authors.forename: Nilsa C
authors.initials: NC
authors.lastname: Ramirez
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Leslie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015820:Cadherins / Q000032:analysis*; D051177:Catenins / Q000032:analysis*; D018797:Cell Cycle Proteins / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins; D051177:Catenins; D018797:Cell Cycle Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; C062521:RCC1 protein, human