Determination of p53 protein and high-risk human papillomavirus DNA in carcinomas of the renal pelvis and ureter.

The presence and distribution of high-risk human papillomavirus (HPV) DNA type-16 and -18 or overexpression of the p53 protein were determined in 31 patients with renal pelvic and ureteral carcinoma in Saga prefecture of Japan, consisting of 28 transitional cell carcinomas (TCCs) and 3 squamous cell carcinomas (SCCs). In situ hybridization with DNA probes for HPV-16 and -18 was performed as well as immunohistochemical techniques using antibody to p53 protein. Fresh tumor tissues from 8 patients were also studied for p53 mutations in exons 5 through 8 by direct sequencing. Of 28 TCC patients at Saga prefecture in Japan, 10 tested were positive for HPV DNA, 5 for HPV type-16, 4 for HPV type-18 and one doubly-positive case. Of the remaining 18 tumors, seven showed positive nuclear staining in cancer cells with p53 antibody. One of the 3 patients with SCCs also revealed the nuclear positivity of the cancer cells with p53 antibody but not with HPV infection. p53 point mutation was detected in 2 cases also showing p53 immunopositivity. Overexpressed p53 protein was statistically more common in invasive and non-papillary (p<0.05) and in high-grade TCCs (p<0.05). These findings suggest that HPV infection, and expression (mutation) of p53 protein may be intimately related to the pathogenesis of urothelial tumor cell growth and progression.