Around 80~90 of cervical carcinomas contain human papillomavirus (HPV) DNA, most frequently oncogenic HPV 16 or 18 HPV E6 and E7 proteins have been shown to have transformation properties. It has been shown that the E6 proteins of the oncogenic
HPVs
that bind p53, having tumor suppressor activities, stimulate the degradation of p53 using ubiquitin-dependent protease system. Also analysis of mutation and expression of the p53gene in cervical carcinoma cell lines has revealed an inverse
relation
between HPV positivity and p53 point mutation/expression. And thus it is suggested that alterations of the p53 gene induced either by mutation or complex formation with HPV E6 protein may be involved in the cervical tumorigenesis. However, the
studies
of primary cervical carcinoma samples have revealed conflicting results. Furthermore some recent data suggested that the alteration of the p53 gene may be involved in the progression of invasive cervical cancer, such as lymph node metastasis.
In this study paraffine-embedded cancer tissue samples derived from 38 women with primary cancer of the cervix were analyzed for presence of HPV 16/18, mutation and expression of the p53 gene. The polymerase chain reaction(PCR) with HPV type
specific
primer and β-globin primer for internal control showed that 78.9%(30/38) of the tumors were HPV 16 or 18 positive. Because the exons 5-9 of the p53 gene are frequently the sites of mutations in many human tumors, analyses of the p53 gene
mutation
were
focused on these sites. Only one HPV-16 positive tumor(2.6%) showed an abnormal shifting pattern in exon 6 by PCR -single strand conformation polymorphism (SSCP). Overexpressed p53 protein was detected in 15.8%(6/38) of the tumors by
immunohistochemistry using monoclonal antibody DO7. No significant correlation between HPV positivity and the expression pattern of p53 gene. Overexpression of the p53 gene was, however, detected in less than 5% of the cells except one case
showing
abnormal SSCP pattern. So another control study was done to establish the minimal proportion of mutant alleles of the p53 gene(confirmed mutation sat exon 7 and 8 at sites, cervical cancer cell lines HT3 and C33A respectively ) mixed with wild
type
alleles(confirmed wild type of the p53 gene, cervical cancer cell lines HeLa land Caski) detected by PCR-SSCP and showed that PCR-SSCP detected 5% mutant alleles. HPV-positive tumor with p53 mutation was overexpressed in more than 20% of the
cells
and a
metastatic lesion.
These data showed no specific association between HPV positivity and alteration of the p53 gene. So HPV E6/p53 interaction may not be an essential step in cervical tumorigenesis.
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