Human Papillomavirus Infection and Expression of Cyclin D1 in the Uterine Cervical Neoplasia

Kim, Min Kwan; Kim, Hee Bum; Lee, Seul Kee; Sunwoo, Jae Gun; Bae, Dong Han; Kim, Chang Jin

Abstract

About 80 subtypes of human papilloma viruses(HPVs) were known, and they were divided into two groups as 'high-risk HPVs' and 'low-risk HPVs' according to their oncogenic potentialities. Even though the precise pathogenic mechanism of uterine cervical cancer were not elucidated, HPV has been considered as a strong candidate for the cause. The cell cycles are tightly regulated by several cyclins and cyclin dependent kinases. Cyclin D1 is known to regulate cell cycle progression at the G1-S phase checkpoint, and its overexpression in human cells is expected to drive the cells through the G1-S phase transition, thus contributing to oncogenesis. In this study, using total of 50 cases of CIN I, II, III and invasive carcinoma, HPVs were typed by DNA microarray and the expressions of cyclin D1 were studied by immunohistochemistry. The results were as follows: 1. Among a total of 50 cases, HPV infection was noted in 39 cases(78%). The HPV 16 were 17 cases(34%), HPV 58, 8 cases(16%) and HPV 52,4 cases(8%). 2. Among a total of 50 cases, cyclin D1 negative expression was in 18 cases(36%), while positive expression was in 32 cases(64%). 3. Among 39 cases of HPV infection, low expression of cyclin D1 was observed in 36 cases(92.3%), while over-expression of cyclin D1 was noted in 3 cases(7.7%)(p<0.05). Above results show that the most frequent HPV type in uterine cervical squamous neoplastic lesion was HPV 16 and the next one was HPV 58. The mixed infection of HPV types were not infrequent. And low expression of cyclin D1 was observed in the lesion infected by high risk HPV, which suggests that the high risk HPVs would affect the amplification of cyclin D1 gene but the gene may produce a modified protein that is not stained with ordinary method or lost the ability to produce cyclin D1.