P53 AND HUMAN PAPILLOMAVIRUS DNA IN RENAL PELVIC AND URETERAL CARCINOMA INCLUDING DYSPLASTIC LESIONS

Ninety-eight cases of transitional-cell carcinoma (TCC) of the renal p elvis and ureter, including dysplastic lesions, were studied for tumor incorporation of human papillomavirus (HPV) type-16 and type-18 DNA b y in situ hybridization (ISH) with DNA probes for each HPV viral type. Immunohistochemical analysis of p53 expression was also performed. Fr esh tumor tissues from 26 patients were also studied for p53 mutations in exons 4 through 9 by direct sequencing and for HPV infection by po lymerase chain reaction (PCR). Thirty-two tumors were positive for HPV DNAs, including 6 double-positive cases. Among these tumors, adjacent dysplastic lesions in 21 cases (66%) also revealed identical reactivi ty. Overexpressed p53 was detected in 26 cases. Expression of p53 was also detected in dysplastic lesions in 19 out of these 26 cases (73%). Three cases were positive for both HPV DNA and p53 antibody. p53 poin t mutation was detected in 7 of 26 cases, 6 of which were also positiv e for p53. HPV type-16 DNA was detected in 6 cases by PCR, 4 of which were also ISH-positive. Overexpressed p53 was frequently detected in i nvasive and non-papillary tumors (p < 0.01) and in high-grade tumors ( P < 0.05). HPV infection was more common in non-invasive and papillary tumors (p < 0.05). These findings suggest that HPV infection or overe xpression (mutation) of p53 may be an early event and be related to ph enotypes of tumor-cell growth patterns and progression. (C) 1995 Wiley -Liss, Inc.