- 作者：Wei Wang ; Shixuan Wang ; Xingfu Song ; Ni Sima ; Xinhua Xu ; Aiyue Luo ; Gang Chen ; Dongrei Deng ; Qian Xu ; Li Meng ; et al.
- 关键词：Cellular FLICE-like inhibitory protein ; Human papillomavirus ; E2 gene ; Cervical carcinogenesis
- 刊名：Gynecologic Oncology
- 出版年：2007
- 出版时间：June 2007
- 年：2007
- 卷：105
- 期：3
- 页码：571-577
- 全文大小：285 K
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.