HIGH-RISK HUMAN PAPILLOMAVIRUS INFECTIONS AND OVEREXPRESSION OF P53 PROTEIN AS PROGNOSTIC INDICATORS IN TRANSITIONAL-CELL CARCINOMA OF THE URINARY-BLADDER

Ninety Japanese patients with transitional cell carcinoma of the urina ry bladder were investigated for tumor incorporation of DNA for high-r isk human papillomavirus (HPV) types 16, 18, and 33 by in situ hybridi zation with biotinylated DNA probes. In addition, immunohistochemical analysis of p53 protein expression was performed with an antibody to p 53 protein. Twenty-eight tumors were positive for HPV DNA, and multipl e 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 w ere simultaneously observed in 6 tumors by using a mirror section meth od. The overexpression of p53 protein was frequently detected in invas ive and nonpapillary tumors (P < 0.05) and in high grade tumors (P < 0 .05). In contrast, HPV infection was more common in noninvasive and pa pillary tumors (P < 0.01). The patients with tumors positive for HPV D NA 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 relativel y poor prognosis in patients with transitional cell carcinoma.