Search

Objective. The expression of the CDK inhibitor p27Kip1 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 p27Kip1 was evaluated by immunostaining. Immunohistochemical detection of 8-hydroxydeoxyguanosine (8-OHdG) was considered as marker of oxidative DNA damage in the same tissues.Results. p27Kip1 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%). p27Kip1 and 8-OHdG expression displayed a significant inverse relationship.Conclusions. Expression of p27Kip1 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. [Copyright &y& Elsevier]