HPV Type16/18 Infection and p53 Gene Alteration in Uterine Cervical Carcinoma

Ryu, Mu Hyun; Park, Hyung Gi; Nam, Jong Hee; Jeong, Sang Woo; Lee, Yu Il; Byun, Ji Soo

Abstract

Recent studies of molecular biology have suggested that infection with human papillomavirus(HPV) is implicated in the pathogenesis of cervical carinoma. HPV infection alone, however, does not appear to be sufficient for the process of maliganant transformation, suggesting the requirement of additional cellular events. The mutation of p53, which is involved in negative control of cell proliferation, may play a role in the carcinogenesis of cervical carcinoma. The present study was designed to clarify the association between infection with HPV and p53 alteration in primary carcinoma of human uterine cervix. We investigated 46 prim-ary cervical carcinomas for the presence of HPV DNA by in situ hybridization(ISH) with probe specific for HPV 16/18, and examined the accumulation of p53 protein by immunohis-tochemistry(IHC) and the p53 alteration by polymerase chain reaction-single strand confor-mation polymorphism(PCR-SSCP) using formalin fixed, paraffin -embedded tissue. HPV DNA 16/18 was detected in 18 cases(39.1%) of 46 cervical carcinomas. The accumulation of p53 was identified in tumor cells: low level 43.5%(20/46) and high level 32.6% difference of positive reaction by IHC method. But there was no statistical significant between the infection of HPV and the accumulation of p53(p=0.847). Mutations in exons 4 through 9, where the vast majority of point mutations were reported in human neoplasms, were screened by PCR-SSCP analysis. Altered mobilities of the PCR product of p53 were also found in 9 cases(26.5%) of 34 cervical carcinoma: one in exon 4, four in exon 5/6, two in exon 7, and two in exon 8/9. The mutation of p53 was observed in 41.1%(19/46) respective of the result of IHC and PCR-SSCP, and there was slightly higher p53 alteration in HPV negative cases(23.8%, 11/46) than in HPV positive cases(17.4%, 8/46) without statistical significance(p=0.729). The conclusion of these observations suggests that HPV infection and alteration of p53 may play a critical role in tumorigenesis of carcinoma of the human uterine cervix independently, ant there is important difference in the tumorigenic pathway between two factors.