[Expression and significance of P16INK4A and PTEN in high-risk human papillomavirus-related cervical cancer].
OBJECTIVE
High-risk human papillomavirus (HR-HPV) is the most important etiologic factor for cervical cancer. Recent studies have revealed that abnormal expression of tumor suppressor gene P16INK4A is closely associated with HR-HPV infection during carcinogenesis of cervical epithelium. Tumor suppressor gene PTEN is also involved in cervical tumorigenesis. This study was to investigate the correlations of HR-HPV infection to P16INK4A and PTEN expression and its clinical significance in the carcinogenesis of cervical epithelium.


METHODS
The expression of P16INK4A and PTEN in 30 specimens of normal cervical tissues, 11 specimens of cancer in situ (CIS), and 24 specimens of invasive cervical carcinoma (ICC) was detected by SP immunohistochemistry; 13 types of HR-HPV DNA in these cases were detected by Hybrid Capture 2 (HC-2) assay.


RESULTS
The positive rates of HR-HPV and P16INK4A were significantly higher in ICC and CIS than in normal tissues (91.7% and 90.9% vs. 30.0%, P<0.001; 87.5% and 81.8% vs. 6.7%, P<0.001). Both HR-HPV DNA and P16INK4A overexpression (moderate or strong expression) were observed simultaneously in 21 specimens of ICC and 9 specimens of CIS; they were simultaneously negative in 20 specimens of normal cervical tissues and 1 specimen of CIS and 2 specimens of ICC. Overexpression of P16INK4A was positively correlated to HR-HPV infection in cervical cancer (rs = 0.690, P<0.001). PTEN was moderately or strongly expressed in 26 specimens of normal cervical tissues. The positive rate of PTEN was significantly lower in ICC and CIS than in normal cervical tissues (37.5% and 36.4% vs. 83.3%, P<0.01). No obvious relationship between PTEN and HR-HPV was found (rs = -0.174, P = 0.167).


CONCLUSIONS
P16INK4A is overexpressed in HR-HPV-infected cervical cancer, but its tumor suppressor action might be inhibited. In contrast, the functional down-regulation of PTEN contributes to cervical tumorigenesis through HR-HPV-independent mechanism.
Zhao
Xian-Lan
XL
Department of Obstetrics and Gynecology, The First Affiliated Hospital,Zhengzhou University, Zhengzhou, Henan, 450052, PR China. zxl@9c9c.com.cn
Cheng
Shu-Xia
SX
Kong
Xiang-Dong
XD
D000230:Adenocarcinoma / Q000378:metabolism / Q000821:virology; D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000378:metabolism / Q000821:virology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000821:virology; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000821:virology; D055815:Young Adult
D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human