Further studies are required to determine the biologic role of p53 gene alterations in the development and progression of this disease and to determine whether p53 mutations can be useful as prognostic markers or for the selection of better treatments for prostate cancer patients.
The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV16 infection could participate in p53 inactivation by E6.
Together these findings appear to explain, at least in part, why there has been a wide discrepancy in the reported detection frequency of p53 mutations in prostate cancer specimens.
We studied the role of p53 tumor suppressor gene alteration in prostate cancer progression by demonstrating a difference in abnormal p53 findings between early and hormone refractory disease.
Testing of prostate cancer biopsy specimens from metastatic sites for p53 protein accumulation and gene mutation may provide useful prognostic information and could influence the recommended course of treatment.
The data suggest not only an association of p53 mutation and progression of clinical prostate cancer, but also imply that some other mechanism(s) are at work in latent carcinoma.
Chromosomal deletions and p53 mutations were confined to locally invasive prostatic carcinomas, suggesting that they are associated with the progression of some prostate cancers rather than with tumor initiation.
Deletions of one copy of the Rb and p53 genes are less frequent as are mutations of the p53 gene, and accumulating evidence suggests the presence of an additional tumor suppressor gene on chromosome 17p, which is frequently inactivated in prostate cancer.
This result indicates that p53 mutations may play a role in the progression of a subgroup of prostate cancers in Japanese, as observed for Americans and Europeans.
These data indicate that mutated p53 alleles are quite uncommon in early prostate cancers but are found in 20-25% of advanced cancers, suggesting a role for p53 mutation in the progression of at least a subset of prostate cancers.
Thus, our data suggest that alterations of the p53 gene at the mutational "hot spots" appear to occur infrequently in primary human prostate cancer, but may emerge in later stages of tumor progression.