p16INK4A expression in cervical premalignant and malignant lesions.
p16INK4a is a cyclin-dependent kinase (CDK) inhibitor which decelerates cell cycle by inactivating CDKs that phosphorylate pRb. Human Papillomavirus persistent infection plays an important role on cervical carcinogenesis, mainly by the action of two viral oncoproteins, E6 and E7, which interact with p53 and pRb, respectively. Increasing expression of E6 and E7 in dysplastic cervical cells might thus be reflected by increased expression of p16INK4a. Recent studies revealed that p16INK4a expression could be a marker for dysplastic and neoplastic cervical cells. The aim of this study was to analyze p16INK4a expression in cervical preneoplastic and neoplastic lesions and correlate with lesion grade. Expression of p16INK4a was analyzed by immunohistochemistry. A total of 6 low-grade squamous intraepithelial lesion (LSIL), 21 high-grade squamous intraepithelial lesions (HSIL) and 27 cancer samples were studied. In HPV-positive cervical samples (n=48), p16INK4a expression was observed in 1 of 3 LSIL, in 18 of 19 HSIL and in all 26 cancer cases. These results are in accordance with the hypothesis that functional inactivation of pRb by HPV-E7 protein induces p16INK4a expression in cervical lesions. In our study, a statistically significant association was observed between cervical lesion grade and p16INK4a expression (P<0.001).
Lambert
Ana Paula Franco
AP
Laboratório de Biologia Molecular do Instituto de Pesquisas Biomédicas, Pontifícia Universidade Católica do Rio Grande do Sul, Rua Prof. Cristiano Fischer 1118/201, Jardim do Salso, Porto Alegre/RS, CEP 91410-000, Brazil. analambert@gmail.com
Anschau
Fernando
F
Schmitt
Virgínia Minghelli
VM
D000293:Adolescent; D000328:Adult; D002584:Cervix Uteri / Q000378:metabolism* / Q000473:pathology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000378:metabolism / Q000473:pathology; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000821:virology
D019941:Cyclin-Dependent Kinase Inhibitor p16