P16 INK4A expression in cervical premalignant and malignant lesions

Abstract

p16 INK4a 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 p16 INK4a. Recent studies revealed that p16 INK4a expression could be a marker for dysplastic and neoplastic cervical cells. The aim of this study was to analyze p16 INK4a expression in cervical preneoplastic and neoplastic lesions and correlate with lesion grade. Expression of p16 INK4a 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), p16 INK4a 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 p16 INK4a expression in cervical lesions. In our study, a statistically significant association was observed between cervical lesion grade and p16 INK4a expression ( P < 0.001).