title: Prognostic significance of TRAIL signalling molecules in cervical squamous cell carcinoma.
abstract: OBJECTIVE
  Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that preferentially induces apoptosis in cancer cells while exhibiting little or no toxicity in normal cells. In this study, we evaluated the clinicopathological significance of TRAIL signalling members' expression profiles in cervical squamous cell carcinoma (CSCC).
  
  
  METHODS
  TRAIL, DR5, caspase-8 and cellular FLICE-inhibitory protein (c-FLIP) protein expression was investigated in 72 stage IA2-IIIA CSCC patients using immunohistochemistry. Correlation between protein expression and clinicopathological features, radiotherapy response and survival was statistically analysed.
  
  
  RESULTS
  Positive c-FLIP expression was an independent negative indicator for disease-free survival (DFS) (p=0.015) in multivariate Cox regression analysis. The DR5 nuclear positive group (p=0.069 by log rank test) showed some advantage of radiotherapy for overall survival (OS) compared with the DR5 nuclear negative cohort (p=0.568 by log rank test). In addition, loss of TRAIL expression was associated with worse differentiation (p=0.004), while absence of caspase-8 staining was more frequently observed in cases with lymphovascular invasion (p=0.035).
  
  
  CONCLUSIONS
  High c-FLIP expression is shown to be an independent prognostic variable, DR5 nuclear expression may serve as a predictive biomarker for radiotherapy, and TRAIL as well as caspase-8 loss may be associated with malignant progression.
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yao
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: Department of Pathology, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Yuxiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Ren
authors.affiliation: Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China.
authors.forename: Congrong
authors.initials: C
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D053181:Caspase 8 / Q000032:analysis*; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018714:Radiotherapy, Adjuvant; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis*; D012307:Risk Factors; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000032:analysis*; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C114109:TNFRSF21 protein, human; C505653:TNFSF10 protein, human; C505530:CASP8 protein, human; D053181:Caspase 8
keywords: CERVICAL CANCER; GYNAECOLOGICAL PATHOLOGY; IMMUNOHISTOCHEMISTRY