ras, p53 and hpv status in benign and malignant prostate tumors

Abstract

To study the role of ras, p53 genes and HPV virus (16 and 18) in the development of prostate cancer, we analyzed tissue sections from 27 patients affected with carcinomas (stages A to D) and from 24 patients with adenomas. Mutations of H, K and N-ras and p53 (exons 2-9) were studied by SSCP and DNA sequencing. Accumulation of p53 protein was studied by immunohistochemistry on tissue sections. Tumors were also analyzed for the presence of HPV16 and -18 sequences by PCR and DNA hybridization with sequence-specific oligonucleotides. No mutation was found in the three ras genes studied, either in carcinomas or adenomas. By SSCP analysis we identified p53 mutations in only 2 of 19 carcinomas studied, both in exon 7. Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+. Among these I presented a p53 mutation. No HPV18 E6 sequence could be detected. Our data show that in prostate tumors from France, mutations of p53 and ras are rare events but that these tumors display detectable HPV16 DNA at a high frequency. 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.

Association between human papillomavirus and prostate cancer: A meta-analysis

“…These studies were published between 1990 and 2015 and comprised 971 PCa cases in total. The majority of the studies originated from Asia (n=8) (38,40,(43)(44)(45)48,51,56), Europe (n=7) (22,39,42,47,50,53,55) and North America (n=5) (23,49,52,54,57), and the remaining studies originated from South America (n=1) (46) and Oceania (n=2) (6,41 Table I. Characteristics of studies included in the meta-analysis.…”

“…others use frozen sections (6,22,23,43,47,(49)(50)(51)(53)(54)(55). A total of 2,056 cases were included in the 24 studies investigating the association between HPV infection and risk of PCa (971 were in the case group and 1,085 were in the control group).…”

Genetic aspects of prostate cancer

“…The role of HPV in prostate cancer is controversial [50, 150,157,182]. The observed HPV viral sequences in prostate tumours could be due to contamination by urethral cells, which form a reservoir for HPV [229].…”

Alteration of the<i>p53</i>Tumor Suppressor Gene in Prostate Cancer: Analytical Approaches and Clinical Implications

“…The moleculargenetic analysis should best be performed in tumor cells microdissected according to the result of the immunohistochemical staining reaction in order to confirm the specificity of immunohistochemistry and to determine whether specific mutations at certain locations are associated with a different clinical course. However, immunohistochemically detected overexpression of a stabilized but in part inactivated wild-type p53 protein, possibly due to the binding of viral proteins such as the E6 and E7 protein of HPV16/18 without a concomitant mutational event at the p53 gene locus may also be of importance [54,55]. Thus, the influence of posttranslational events on the protein level may be detectable by an immunohistochemical approach and can also be included in the analysis of prognostic factors for the clinical course.…”