Clinical Significance of p27 and Skp2 Protein Expression in Uterine Cervical Neoplasm

Abstract

The loss of p27 indicates a poor prognosis in various solid tumors, and a decrease in p27 level is the result of increased degradation by Skp2. We evaluated the relationship of p27 and Skp2 protein expression to various clinicopathologic factors in 332 cases of untreated uterine cervical neoplasm using tissue microarray method. After immunohistochemical staining, 313 and 300 tumor samples were retrieved for interpretation for p27 and Skp2, respectively. High p27 protein expression (nuclear staining in more than 30% of the tumor cells) was seen in 39.9% (125/313 cases), including 32 cervical intraepithelial neoplasia (CIN) III (55.2%), 58 microinvasive squamous cell carcinoma (SCC) (56.9%), 21 invasive SCC (17.1%), 11 adenocarcinoma (55.0%), and 3 cases of other tumors (30.0%). High Skp2 protein expression was noted in 28.3% (85/300 cases), including 14 cervical intraepithelial neoplasia III (25.0%), 18 microinvasive SCC (18.75%), 45 invasive SCC (37.8%), 6 adenocarcinoma (30.0%), and 2 cases of other tumors (22.2%). Low p27 protein expression was correlated with large tumor size (P < 0.005), depth of invasion in squamous lesion (P < 0.0005), high stage (P < 0.0005), and poor survival (P < 0.005). High Skp2 protein expression was correlated with large tumor size (P < 0.05), depth of invasion in squamous lesion (P < 0.05), and high stage (P < 0.005), but not with patient survival. There was no significant correlation between p27 and Skp2 protein expression. Only tumor stage had prognostic significance in the multivariate analysis (P = 0.041). Patients with low p27 protein expression had worse prognosis, indicating that p27 may participate in the progression of cervical squamous cell lesions.