ИСТИНА

Background. The problem of whether or not human papillomaviruses (HPVs) take part in malignant transformation of urothelium has both theoretical and practical aspects. To specify the carcinogenic potential of these viruses, it is needed to understand if they can transform specific epithelial cell types, in particular, bladder transitional cells (urothelium). Preliminary evidence for a group of HPV-positive bladder cancers (BCs) has been supported by clinical peculiarities of these patients. Discrepancy of data may result from ethno-geographic variabilities of the disease and/or different technical approaches used by researchers. In the majority of studies that confirmed the role of HPVs in BC, viral DNA was found in the tumor specimens largely by PCR or in situ hybridization. Previously we detected HPV DNA by in situ hybridization in ~50% of transitional cell BC specimens [1]. However, the expression of the viral genome was not evaluated. Objective of the present study was to verify the hypothesis on HPVs’ participation in urothelial carcinogenesis in Russia. Methods. Diagnostics was done by two independent pathologists (A.Y.Y.,E.V.D). RNA was isolated from frozen cancer tissue; RT-PCR and immunohistochemistry carried out as described earlier [2-5]. Results. The expression of HPV type 16 E6 and E7 oncogenes was registered by RT-PCR in 8 out of 30 transitional cell BCs studied (26.8%). This result was confirmed by immunohistochemical staining with antiserum to E7 HPV16. Positively stained cancer cells formed small groups among HPV-negative cancer cells. Thus, the patterns of staining differed from those described by us for HPV-positive squamous cell cervical carcinomas where E7 was detectable in each tumor cell, although in various amounts [4]. Furthermore, overexpression of the cellular protein p16INK4a (an inhibitor of the cyclin dependent kinases, Cdks 4/6) is a recognized indicator of the HPV-induced cervical carcinogenesis [3,4]. By staining with p16INK4a-specific monoclonal antibody we found no positive cells in specimens where HPV 16 oncogenes were expressed. Thus the applicability of this marker for urothelial carcinogenesis remains to be elucidated. Conclusion. Our resuls are in agreement with the notion that HPVs play a role in malignant transformation of urothelium. The hypothesis seems to deserve further verification.