title: Prognostic and predictive values of Nrf2, Keap1, p16 and E-cadherin expression in ovarian epithelial carcinoma.
abstract: OBJECTIVE
  Despite considerable interest in the Nuclear factor-erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein-1 (Keap1), p16 and epithelial cadherin (E-cadherin) activation in carcinoma progression, contradictory results regarding association of Nrf2/Keap1/E-cadherin and p16 expression with clinico-pathological features and prognosis have been reported. The predictive value of these markers in ovarian carcinoma is unknown.
  
  
  METHODS
  In this retrospective study, 108 cases were evaluated immunohistochemically with antibodies to Nrf2, Keap1, estrogen receptor (ER), p16 and E-cadherin. The results were compared with histological and clinical data, disease-free survival (DFS) and overall survival (OS).
  
  
  RESULTS
  A cohort of 108 ovarian carcinomas (47 serous, 23 mucinous, 13 endometrioid and 25 clear cell), including 68 FIGO stage I-II cases and 40 FIGO stage III-IV cases was studied. The age of patients (P=0.005), FIGO stage (P<0.001), immunohistochemical expression of Keap1 (P<0.000), E-cadherin (P=0.045), p53 (P=0.003), p16 (P<0.001) and ER (P=0.004) were significant factors between different histological subtypes. Patients with serous carcinoma were older in age, presented with more advanced stage disease, worst prognosis, highest Keap1 expression and least percentage of E-cadherin immunoreactivity. In univariate analysis, FIGO staging (P=0.000 for DFS; P=0.000 for OS), Nrf2 (P=0.010 for DFS; P=0.001 for OS), and p16 (P=0.004 for DFS; P=0.019 for OS) were associated with worse prognosis. After multivariate analysis, FIGO staging and Nrf2 remained significance prognostic factors.
  
  
  CONCLUSIONS
  There were differences in the expression of Nrf2, Keap1, p16 and E-cadherin between different ovarian carcinoma subtypes. In multivariate analysis, FIGO stage and Nrf2 expression were associated with poorer DFS and OS.
authors.affiliation: Department of Pathology, Shuang Ho Hospital, Taipei Medical University Taipei, Taiwan ; Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan.
authors.forename: Phui-Ly
authors.initials: PL
authors.lastname: Liew
authors.affiliation: Department of Obstetrics and Gynecology, Wan Fang Hospital, Taipei Medical University Taipei, Taiwan.
authors.forename: Chun-Sen
authors.initials: CS
authors.lastname: Hsu
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Medical University Hospital, Taipei Medical University Taipei, Taiwan.
authors.forename: Wei-Min
authors.initials: WM
authors.lastname: Liu
authors.affiliation: Graduate Institute of Medical Sciences, Taipei Medical University Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of International Business, Chien Hsin University of Science and Technology Zhongli City, Taiwan.
authors.forename: Yi-Chih
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University Taipei, Taiwan ; Department of Pathology, Taipei Medical University Hospital, Taipei Medical University Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000032:analysis*; D015820:Cadherins / Q000032:analysis*; D000077216:Carcinoma, Ovarian Epithelial; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000032:analysis*; D053208:Kaplan-Meier Estimate; D000072019:Kelch-Like ECH-Associated Protein 1; D016015:Logistic Models; D008875:Middle Aged; D015999:Multivariate Analysis; D051267:NF-E2-Related Factor 2 / Q000032:analysis*; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D047908:Intracellular Signaling Peptides and Proteins; C431364:KEAP1 protein, human; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human
keywords: E-Cadherin; Keap1; Nrf2; ovarian cancer; p16