The Relationship of HPV Infection with Ki-ras and p53 Mutation in Uterine Cervical Carcinomas

Choi, Kyu Yeon; Bae, Dong Han; Kim, In Sun

Abstract

OBJECTIVE
Human papillomavirus(HPV) is an important pathogenetic agent in the uterine cervical carcinoma. It has been known that E6 and E7 proteins of high risk HPV viruses abolish the action of tumor suppressor genes, Rb and p53, resulting in cellular proliferation. This study was designed to determine the incidence of Ki-ras and p53 mutations in uterine cervical carcinomas and evaluate the results of mutations according to the status of HPV infection.
METHODS
Paraffin-embedded tissue samples obtained from 42 CIN III and 70 invasive carcinomas of the uterine cervix(56 squamous, 7 adenosquamous and 7 adenocarcinomas). Ki-ras codon 12 mutation was analysed by PCR-RFLP method and p53 exons 5, 6, 7 and 8 mutations by PCR-SSCP. The presence of HPV was detected by PCR using consensus primers for high risk viruses(HPV 16, 18, 31, 33, 35, 52b, and 58) and low risk viruses(HPV 6 and 11).
RESULTS
HPV viruses were detected in 83.3% of CIN III and 90% of invasive carcinomas; 71.4% of adenocarcinomas, 91.7% of squamous cell carcinomas and 100% of adenosquamous carcinomas. Ki-ras codon 12 mutation was detected in 4.7% of CIN III and 11.4% of invasive carcinomas, and p53 mutations in 4.8% of CIN III and 7.1% of invasive carcinomas. There was no significant difference of Ki-ras mutation between HPV-positive group(9.2%) and HPV-negative group(7.1%). However, p53 mutation was more frequent in HPV-negative group(28.6%) than HPV-positive group(3.1%). (p=0.0002)
CONCLUSIONS
HPV is an agent which is detected in high frequency of uterine cervical carcinomas and p53 mutation may have a role in the HPV-negative uterine cervical carcinomas. However, the relationship between Ki-ras gene and HPV in uterine cervical carcinogenesis remains to be defined.