Аннотация:Background: Cellular protein p16INK4a inhibits cyclin-dependent kinase 4 and 6. The p16INK4a overexpression, a recognized marker of HPV-induced cervical carcinogenesis, is currently widely used for early diagnostics of cervical cancer. In many tumor types including bladder cancer the gene INK4a coding for p16INK4a is detected or harbors point mutations or is inactivated epigenetically. Many authors argue that HPVs participate in bladder urotelium carcinogenesis. To study clinical peculiarities of HPV-positive bladder cancer, knowledge about its cellular marker is needed. The aim of the present study was to analyze whether p16INK4a is applicable as a marker of HPV-associated urotelium carcinogenesis.
Design: Formalin fixed and paraffin embedded tumor tissue from 50 patients with bladder invasive urothelial carcinoma (G1 – G3) were examined by immunohistochemistry to analyze expression of p16INK4a and virus oncogene E7. 30 cases from this group by RT-PCR were studied to analyze expression HPV16 E6 and E7 mRNA by RT-PCR .
Results: We observed positive staining with monoclonal antibody to p16INK4a in 5 cases from 50 (10%). Reaction was localized in nuclei and cytoplasm of tumor cells. 8 speciments from 30 previously shown to express HPV E6 and E7 mRNA by RT-PCR. 5 speciments from last group shown to express oncoprotein E7 by immunohistochemistry. Positive staining was focally in tumor tissue. But, there was no p16INK4a expression in there E6 – E7 mRNA positive samples.
Conclusion: Thus, p16INK4a overexpression cannot serve as an indicator of the HPV oncogene-expressing bladder cancer. The nature of p16INK4a positivity in urothelial cancer remains to be further studied.
Acknowlegement: The study is supported by the Russian Foundation of Basic Research, grand № 07-04-00800-а.