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

Aim—To investigate whether there is loss of the p27 protein in developing cervical cancer and whether p27 immunoreactivity has any relation to the proliferative indicator Ki-67. Methods—The expression of p27 and Ki-67 was assessed by immunohistochemistry 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 papillomavirus (HPV) genomic sequences was assessed by in situ hybridisation. The results were evaluated by image analysis, and reported as mean score of the percentage of p27 and of Ki-67 positive cells in each histological group. Results—In general, p27 immunostaining was related to squamous diVerentation, and was intense in normal epithelium (47%), while it was reduced in SIL lesions as an eVect of the decreased number of diVerentiating cells. However, decrease in the p27 expression was more evident in LSIL (36%) than in HSIL (39%); in the latter, p27had a diVerent intraepithelial distribution in that the staining extended to the basal cells. The average levels of p27 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 levels (23%). There was no relation between p27 and Ki-67 labelling indices in any of the histological groups examined. Conclusions—A reduction in p27 protein occurs in cervical cancer independently of the proliferative status. The changes in p27 expression may be related to the unregulated kinetics of developing cervical cancer. (J Clin Pathol 1999;52:880–887)