Decreased expression of the CDK inhibitor p27 Kip1 and increased oxidative DNA damage in the multistep process of cervical carcinogenesis

Abstract

Objective. The expression of the CDK inhibitor p27 Kip1 and the extent of endogenous oxidative DNA damage were evaluated in the multistep cervical carcinogenesis. Methods. Archival specimens of low-grade (L) squamous intraepithelial lesions (SILs) ( n = 32), high-grade (H) SILs ( n = 24) and invasive carcinomas ( n = 48) of the cervix were included in the analysis compared with normal cervical squamous epithelium ( n =15). Expression level of p27 Kip1 was evaluated by immunostaining. Immunohistochemical detection of 8-hydroxydeoxyguanosine (8-OHdG) was considered as marker of oxidative DNA damage in the same tissues. Results. p27 Kip1 was constantly expressed in normal epithelium with a mean percentage of positive cells higher than 50%. A progressive significant reduction in the mean percentage of positive cells was observed in L-SIL (18.1%), H-SIL (7.3%) and in invasive carcinomas (2.5%). A progressive significant increase in the levels of 8-OHdG and in the percentage of mean positive cells was observed from L-SIL (2.2%) to H-SIL (12.5%) to invasive carcinomas (25.2%). p27 Kip1 and 8-OHdG expression displayed a significant inverse relationship. Conclusions. Expression of p27 Kip1 is down-regulated while oxidative DNA damage increases during cervical carcinogenesis. Both parameters are altered at early stages of the process and might help to predict patients at high risk of progression.