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High-Risk Human Papillomavirus Infections and Overexpression of p53 Protein as Prognostic Indicators in Transitional Cell Carcinoma of the Urinary Bladder¹

Second Department of Pathology and Department of Urology, Kochi Medical School, Nankoku, Kochi 783, [M. F., K. I, Y. O., Y. F.], and Division of Urology, Kochi Takasu Hospital, Kochi 780 [H. H., N. T.], Japan

Ninety Japanese patients with transitional cell carcinoma of the urinary bladder were investigated for tumor incorporation of DNA for high-risk human papillomavirus (HPV) types 16, 18, and 33 by in situ hybridization with biotinylated DNA probes. In addition, immunohistochemical analysis of p53 protein expression was performed with an antibody to p53 protein. Twenty-eight tumors were positive for HPV DNA, and multiple HPV infection was detected in 17 cases. Positive nuclear staining of cancer cells by the antibody to p53 protein was detected in 32 cases. DNA for HPV 16, 18, and/or 33 and the overexpression of p53 protein were simultaneously observed in 6 tumors by using a mirror section method. The overexpression of p53 protein was frequently detected in invasive and nonpapillary tumors (P < 0.05) and in high grade tumors (P < 0.05). In contrast, HPV infection was more common in noninvasive and papillary tumors (P < 0.01). The patients with tumors positive for HPV DNA and/or p53 antibody had a significantly worse survival rate (P < 0.05). These results suggest that HPV infection or overexpression of p53 protein may be related to tumor behavior and may indicate a relatively poor prognosis in patients with transitional cell carcinoma.

¹ This work was supported in part by Grants-in Aid for Encouragement of Young Scientists from the Ministry of Education, Science and Culture of Japan.

² To whom requests for reprints should be addressed, at Kochi Medical School, 2nd Department of Pathology, Nankoku, Kochi 783, Japan.

Received 4/29/93. Accepted 8/ 9/93.

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