P53 ACCUMULATION, DEOXYRIBONUCLEIC-ACID PLOIDY AND PROGRESSION OF BLADDER-CANCER

Purpose: The alterations in deoxyribonucleic acid (DNA) ploidy and p53 expression during progression of bladder cancer were determined. Mate rials and Methods: p53 Expression and DNA ploidy were studied in 51 pa tients with transitional cell carcinoma of the bladder (mean followup 5 years). Of 29 primarily superficial tumors (stages Ta and T1) 17 bec ame subsequently invasive (greater than stage T2) within an average of 4 years (group 2) and 12 recurred superficially with no sign of progr ession during a mean followup of 10.8 years (group 1). Of the patients 22 had metastatic disease (group 3). Samples of tumors at diagnosis a nd recurrence or progression were analyzed by immunohistochemistry and flow cytometry. Results: p53 Accumulation was detected at diagnosis i n 29 of the 51 patients (57%), including 3 of 12 (25%) in group 1, 5 o f 17 (29%) in group 2 and 14 of 22 (64%) in group 3. The p values for the differences between groups 1 and 3, and 2 and 3 were 0.07 and 0.05 4, respectively. Abnormal DNA contents were noted in 3 of 12 (25%), 11 of 17 (65%) and 16 of 22 (73%) patients in groups 1 to 3, respectivel y, and the differences between groups 1 and 2, and 1 and 3 were statis tically significant. Using these 2 genetic markers, we found genetic p rogression to be uncommon in groups 1 and 3, whereas in group 2 an ini tially negative p53 staining became positive at invasion into the musc le in 5 of 12 patients (42%). Conclusions: The tumors in patients with superficial recurrences are mostly diploid and negative for p53, and those with metastasis are nondiploid and positive for p53 from the beg inning, while further genetic progression is uncommon. However, p53 te nds to accumulate frequently when the tumor begins to invade the muscl e. There seems to be a need for caution against under staging an appar ent stage T1 tumor that is positive for p53.