Cyclin dependent kinase inhibitor p27(Kip1) expression in normal and neoplastic cervical epithelium

Aim-To investigate whether there is loss of the p27(Kip1) protein in develo ping cervical cancer and whether p27(Kip1) immunoreactivity has any relatio n to the proliferative indicator Ki-67. Methods-The expression of p27(Kip1) and Ki-67 was assessed by immunohistoch emistry in serial sections from normal epithelium (13), low grade (27) and high grade (19) squamous intraepithelial lesions (LSIL, HSIL), and invasive cervical cancer (23). In the SIL cases the presence of human papillomaviru s (HPV) genomic sequences was assessed by in situ hybridisation. The result s were evaluated by image analysis, and reported as mean score of the perce ntage of p27(Kip1) and of Ki-67 positive cells in each histological group. Results-In general, p27(Kip1) immunostaining was related to squamous differ entiation, and was intense in normal epithelium (47%), while it was reduced in SIL lesions as an effect of the decreased number of differentiating cel ls. However, decrease in the p27(Kip1) expression was more evident in LSIL (36%) than in HSIL (39%); in the latter, p27(Kip1) had a different intraepi thelial distribution in that the staining extended to the basal cells. The average levels of p27(Kip1) were similar in SIL lesions associated to low, intermediate, and high risk HPV types. Compared with normal epithelium and dysplasia, invasive cancer showed significantly lower p27(Kip1) levels (23% ). There was no relation between p27(Kip1) and Ki-67 labelling indices in a ny of the histological groups examined. Conclusions-A reduction in p27(Kip1) protein occurs in cervical cancer inde pendently of the proliferative status. The changes in p27(Kip1) expression may be related to the unregulated kinetics of developing cervical cancer.