A study on expression of Human Papillomavirus 16/18, E6/ E7 and Ki-67 in the cervical cancer

Bae, Dong Han; Kim, Min Kwan; Jang, Kyung Tak

Abstract

The squamous cell carcinoma of the uterine cervix is the most common malignant tumor among women in Korea. Since 1976, when a research result that human papillomavirus(HPV) infection played some role in the carcinogenesis of the uterine cervical carcinoma had been published, numerous reports supporting the result have been released. Among the types of the HPV, type 16 and type 18 are classified as high risk types because they are frequently found in cervical lesions with high grade dysplasia and invasive carcinomas. However, it is impossible to ascertain by host histologic or cellular changes which type of HPV is infected. The HPV genome is composed of six open reading frames (ORF' s) named as E1, E2, E4, E5, E6 and E7 in the early region. Among these oncoproteins HPV E6/E7 have been strongly suggested to be important in carcinogenesis. When HPV infects the epithelial cells, it promotes cellular proliferation. The cellular proliferation can be evaluated by immunohistochemistry with the antibodies for proliferating cell nuclear antigen(PCNA) and Ki-67. Because PCNA has long half-life, and can be detected 48 hours after completion of mitosis, an estimation of proliferating cells by PCNA could be inaccurate. The expression of Ki-67 antigen is more correct than PCNA for the evaluation of proliferation cells due to its short half-life and rapid degradation after completion of the mitosis. In this study, immunohistochemical staining was conducted to determine the rate of expression of HPV E6, E7 and Ki-67, correlation with relationship in carcinoma in situ and invasive uterine cervical cancer. Fifty cases of carcinoma of in situ(CIS) and invasive carcinoma were immunohistochemically stained, and the results obtained were as follows: 1) E6 protein of HPV type 16/18 was expressed in 5 of 14 cases(35.7%) of carcinoma in situ, in 3 of 7 cases of microinvasive carcinoma (42.8%) and in 12 of 20 cases of invasive carcinoma(60%) but there was no significant difference in expression between the carcinoma in situ and invasive cancer group (p=0.138). 2) E7 protein of HPV type 16/18 was expressed in 10 of 14 cases(71.4%) of carcinoma in situ, in 6 of 7 cases of microinvasive carcinoma (85.7%), and in 18 of 20 cases of invasive carcinoma(90%) but there was no significant difference in expression between the carcinoma in situ and invasive cancer group (p=0.138). 3) The cell fraction expressing Ki-67 was expressed in 5 of 14 cases(35.7%) of carcinoma in situ, in 5 of 7 cases of microinvasive carcinoma (71.4%), and in 18 of 20 cases of invasive carcinoma.(90%) The cell fraction expressing Ki-67 increased according to the progress of cervical cancer. 4) There was no statistical significance between HPV type 16/18 E6 protein and the cell fraction expressing Ki-67(p=0.09). 5) There was no statistical significance between HPV type 16/18 E7 protein and the cell fraction expressing Ki-67(p=0.17). The above results suggest that the cell fraction expressing Ki-67 increases according to the invasiveness of cervical cancer and E6/E7 protein seem to play a role in the progression of cervical cancer. However we were not able to reveal a relation between E6/E7 protein and the cell fraction expressing Ki-67 in progress of cervical carcinoma, and it is recommended that further studies should be undertaken.