Our data suggest that loss of wild-type p53 function is important in development of cervical carcinoma, and that this might be achieved either by mutation within the p53 gene or the presence of a virally encoded p53 binding protein.
Although a high incidence of HPV DNA integration and a low incidence of p53 mutation were confirmed in cancer of the uterine cervix, there was no inverse association between integration of HPV types 16 and/or 18 DNA and p53 mutation.
The inactivation of the wild-type p53 function resulting from a missense mutation, or the lack of detectable wild-type p53 protein due to the translational/post-translational deregulation of p53 protein levels may be the contributing factor in the tumorigenicity of these five cases of cervical cancer.
Our data indicate that loss of wild-type p53 function is important in the pathology of cervical cancer and that in the absence of an HPV-encoded gene product that mediates loss of p53 function, somatic mutation of the gene is required.
Inactivation of the protein product of the wild-type tumour suppressor gene p53 through complexing of the protein with the E6 oncoprotein of human papillomaviruses (HPV) in HPV-infected cells is thought to be important in the aetiology of cervical carcinoma.
It appears that p53 and Rb mutations are a very rare event in cervical cancer and their occurrence is apparently not strictly correlated with HPV status.
Following these results, immunohistochemistry with the PAb monoclonal antibody may be safely used as a screening tool for the detection of mutated p53 in clinical samples of mammary and endometrial cancer, whereas it should be complemented with DNA analysis in cervix carcinoma.
In summary, although inactivation of p53 mediated either by E6 or by mutations may be an important key step in the development of cervical carcinoma, our study suggests that other mechanisms may also be involved in development of cervical cancer.
Because most HPV-positive cervical carcinoma cell lines contain wild-type p53 whereas HPV-negative cell lines have point mutations in the p53 gene, a major role in the development of HPV-negative cervical cancer has been attributed to p53.
Our results support the previous reports that the dysfunction of p53 plays an important role in the development of cervix cancers but contrary to the results obtained from cervix cancer all lines, there is no inverse correlation between HPV infections and p53 mutations in primary cervix cancers.
These data suggest that transfection of HPV-positive cervical cancer cells with a wild-type p53 gene in a form such as Ad5CMV-p53 is a potential novel therapy for cervical cancer.
These results indicate that transfection of cervical cancer cells with the wild-type p53 gene via Ad5CMV-p53 is a potential novel approach to the therapy of cervical cancer.