Expression of Cyclin Dependent Kinase (CDK) Inhibitors in Cervical Carcinoma

Kim, Young Tae; Park, Sang Won; Kim, Jae Wook; Cho, Nam Hoon

Abstract

Recent studies have revealed a new family of tumor suppressor genes that directly implicate aberrant cell cycle regulation in tumorigenesis. The general function of these gene products is that they prevent cell cycle progression by directly interfering with cyclin/cyclin dependent kinase (CDK) activation. The importance of these genes is that they are potent inhibitors of CDK and are induced by p53. Among these cell cycle inhibitors, p21WAF1/CIP1 and p16 have been thoroughly studied. However, the role of p21WAF1/CIP1 and p16 in tumorigenesis of the uterine cervix has been poorly defined. We used immunohistochemical techniques to study the expression of these cell cycle inhibitors in formalin-fixed, paraffin-embedded cervical tissue to explore the relationship between cyclin/CDK inhibitors and cervical carcinoma. Cervical tissues were analyzed from 46 patients with cervical carcinoma, 30 cases with cervical intraepithelial neoplasia (CIN) and 22 control cases who underwent hysterectomy due to benign gynecologic disease at Yonsei University College of Medicine. All CDK inhibitors strongly expressed in the reverse cell hyperplasia and koilocytes, whereas they revealed significantly decreased expression in neoplastic tissues (p<0.05). Normal endocervical cells revealed focal and weak expression to all CDK inhibitors but p16 showed no expression in endocervical adenocarcinoma. P16 revealed higher expressions in cases associated with human papilloma virus (HPV) (t-test, p<0.05) than in cases lacking any type of HPV. Our results were consistent with the concept that underexpression of CDK inhibitors may play an important role in neoplastic transformation in cervical carcinoma.