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Prognostic significance of TRAIL signalling molecules in cervical squamous cell carcinoma
  1. Qian Yao1,
  2. Juan Du1,
  3. Jie Lin2,
  4. Yiming Luo1,
  5. Yuxiang Wang1,
  6. Yan Liu1,
  7. Bo Zhang1,
  8. Caixia Ren3,
  9. Congrong Liu1
  1. 1Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, Beijing, China
  2. 2Department of Pathology, China-Japan Friendship Hospital, Beijing, China
  3. 3Department of Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China
  1. Correspondence to Dr Congrong Liu, Department of Pathology, School of Basic Medical Sciences, Third Hospital, Beijing Key Laboratory of Tumor Systems Biology, Peking University Health Science Center, 38 College Road, Haidian, Beijing 100191, China; congrong_liu{at}hsc.pku.edu.cn

Abstract

Aim 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.

  • CERVICAL CANCER
  • GYNAECOLOGICAL PATHOLOGY
  • IMMUNOHISTOCHEMISTRY

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