title: The relationship between c-FLIP expression and human papillomavirus E2 gene disruption in cervical carcinogenesis.
abstract: OBJECTIVE
  Human papillomavirus (HPV) is the essential causative factor in cervical carcinogenesis, and apoptosis inhibition is one of the key features of HPV-induced malignant transformation. This study is to investigate the possible cause-effect association between high-risk HPV and cellular FLICE-like inhibitory protein (c-FLIP), an important apoptosis regulator, during cervical carcinogenesis.
  
  
  METHODS
  A series of 80 archival samples, including 20 squamous cervical carcinomas (SCC) 54 cervical intraepithelial neoplasia (CIN) lesions and 6 normal cervical tissues, were subjected for c-FLIP immunohistochemical staining and HPV HC-II analysis. Typing HPV-16 infection was analyzed by the polymerase chain reaction (PCR), and its status was assessed with the integrity and disruption of the HPV-16 E2 gene, which was amplified in three overlapping fragments.
  
  
  RESULTS
  The types of HR-HPV infection and E2 disruption were associated closely with cervical lesion severity. There was a significant relationship between lesion grade and c-FLIP expression level. c-FLIP overexpression was also closely associated with HR-HPV infection and its integration status. Multivariate regression analysis revealed c-FLIP as a strong independent predictor for CIN, with 100% PPV, and showed 90.9% PPV in detecting HR-HPV, and remained a significance factor to rule out which case has no HR-HPV integration, with a 94.7% sensitivity and a 90.0% NPV.
  
  
  CONCLUSIONS
  The present data approved that c-FLIP overexpression is related significantly to the presence of HR-HPV infection and its integration status during progression of cervical squamous cell cancer and confirmed the role of c-FLIP as an early marker of cervical carcinogenesis.
authors: Cancer Biology Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China.
authors: Wei
authors: W
authors: Wang
authors: Shixuan
authors: S
authors: Wang
authors: Xingfu
authors: X
authors: Song
authors: Ni
authors: N
authors: Sima
authors: Xinhua
authors: X
authors: Xu
authors: Aiyue
authors: A
authors: Luo
authors: Gang
authors: G
authors: Chen
authors: Dongrei
authors: D
authors: Deng
authors: Qian
authors: Q
authors: Xu
authors: Li
authors: L
authors: Meng
authors: Yunping
authors: Y
authors: Lu
authors: Ding
authors: D
authors: Ma
mesh_terms: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009856:Oncogene Proteins, Viral / Q000235:genetics*; D030361:Papillomavirus Infections / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016133:Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D004268:DNA-Binding Proteins; C054855:E2 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral