title: DEF6 expression in ovarian carcinoma correlates with poor patient survival.
abstract: BACKGROUND
  Increased expression of DEF6 is correlated with the malignant behavior of various cancers. Both DEF6 and p16 contribute to the regulation of cell cycle progression, and p53 plays important role in the cell cycle checkpoints. This study was designed to elucidate the prognostic significance of DEF6, p53 and p16 immunoexpressions in different histology subtypes of ovarian carcinoma.
  
  
  METHODS
  Immunohistochemistry results of DEF6, p53 and p16 on ovarian carcinoma were compared with histology subtypes, clinical data, overall survival (OS) and disease-free survival (DFS) by Cox regression and Kaplan-Meier analysis.
  
  
  RESULTS
  We studied 180 cases of ovarian carcinomas (75 high-grade serous, 41 clear cell, 36 mucinous and 28 endometrioid), including 109 FIGO stage I-II cases and 71 FIGO stage III-IV cases. Ovarian carcinomas positive for both DEF6 and p16 expression were associated with the worst OS (P = 0.027) and DFS (P = 0.023), whereas those negative for both DEF6 and p16 had the best OS and DFS. Aberrant p53 expression combined with positive DEF6 was associated with worst OS (P = 0.031) and DFS (P = 0.028). Kaplan-Meier analysis showed that significantly shorter survival rates were seen in patients with high expressions of DEF6 (P = 0.008) and p16 (P = 0.022). Patients with aberrant p53 expression in high-grade serous carcinoma (P = 0.012) and patients with high DEF6 expression in clear cell carcinoma (P = 0.001) were also associated with shorter overall survival. In univariate analysis, FIGO stage, DEF6 and p16 were associated with poor prognosis. DEF6 expression was the only independent prognostic factor correlated with shorted OS (HR 2.115; P = 0.025) and DFS (HR 2.248; P = 0.016) upon multivariate analysis.
  
  
  CONCLUSIONS
  DEF6 expression may serve as an independent prognostic factor, and interacted positively with p16 toward high tumor stage and shorter survival.
authors.affiliation: Department of Pathology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.|Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Xing Street, Taipei, 11031, Taiwan.
authors.forename: Phui-Ly
authors.initials: PL
authors.lastname: Liew
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Xing Street, Taipei, 11031, Taiwan.|Department of Pathology, Wan Fang Hospital, Taipei Medical University, Taipei, 116, Taiwan.
authors.forename: Chih-Yeu
authors.initials: CY
authors.lastname: Fang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of International Business, Chien Hsin University of Science and Technology, Taoyuan, 32097, 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, No. 250, Wu Xing Street, Taipei, 11031, Taiwan. chencl@tmu.edu.tw.|Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan. chencl@tmu.edu.tw.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Pathology, School of Medicine, College of Medicine, Taipei Medical University, No. 250, Wu Xing Street, Taipei, 11031, Taiwan. jschu@tmu.edu.tw.|Department of Pathology, Taipei Medical University Hospital, Taipei Medical University, Taipei, 11031, Taiwan. jschu@tmu.edu.tw.
authors.forename: Jan-Show
authors.initials: JS
authors.lastname: Chu
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D002288:Adenocarcinoma, Mucinous / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018269:Carcinoma, Endometrioid / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D045744:Cell Line, Tumor; D015331:Cohort Studies; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D018293:Cystadenoma, Serous / Q000175:diagnosis / Q000378:metabolism / Q000401:mortality; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D009687:Nuclear Proteins / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality; D011379:Prognosis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C479750:DEF6 protein, human; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53
keywords: Ovarian carcinoma, DEF6; p16, Prognosis