Correlation of Ki-67 and p53 with the New World Health Organization/International Society of Urological Pathology classification system for urothelial neoplasia

Objective.-The present study examines p53 and Ki-67 staining patterns of th e diagnostic entities included within the new World Health Organization/Int ernational Society of Urological Pathology (WHO/ISUP) classification of uro thelial neoplasms. Design.-We retrospectively studied 151 bladder biopsies from 81 patients wi th the following neoplasms: normal urothelium (n = 34 biopsies); low-grade intraurothelial neoplasia (LGIUN; n = 19); high-grade intraurothelial neopl asia (HGIUN; n = 20); papillary hyperplasia (n = 4); papilloma (n = 3); pap illary neoplasm of low malignant potential (LMP; n = 12); low-grade papilla ry carcinoma (n = 28); and high-grade papillary carcinoma (n = 31). Section s were labeled immunohistochemically with antibodies to p53 and Ki-67 (MIB- 1). Two hundred cells from each lesion were visually counted, and the perce ntage of positive cells was tabulated without knowledge of the WHO/ISUP dia gnosis. Results.-In flat lesions, p53 positivity was of limited diagnostic utility; the marker was present in 6 of 34 benign biopsies, 6 of 19 LGIUNs, and 10 of 20 HGIUNs. In one case in which HGIUN was present elsewhere in the bladd er, 29% of the benign urothelial cells were p53 positive. In papillary lesi ons, p53 positivity was not seen in 4 of 4 cases of papillary hyperplasia, 3 of 3 papillomas, and 8 of 12 LMP tumors. In contrast, p53 was detected in 18 of 28 low-grade and 26 of 31 high-grade papillary urothelial carcinomas . A p53 labeling index (LI) greater than 30% was only seen in HGIUNs and hi gh-grade papillary carcinomas. In flat lesions, an increased Ki-67 LI separ ated out benign urothelium (mean LI, 0.62%) from dysplasia (mean LI, 3.3%) and HGIUN (mean LI, 11.6%). In papillary lesions, Ki-67 positivity was as f ollows: papillary hyperplasia (mean LI, 1.1%); papilloma (mean LI, 4.3%); L MP tumors (mean LI, 2.5%), low-grade papillary carcinoma (mean LI, 7.3%); a nd high-grade carcinoma (mean LI, 15.7%). A Ki-67 LI greater than 10% was s een only in low- and high-grade papillary carcinomas, HGIUN, and single cas es of LGIUN and papillary neoplasm of LMP. Conclusions.-An increased proliferative index as demonstrated by immunohist ochemical staining for Ki-67 (MIB-1) is most often seen in papillary carcin oma and HGIUN. Marked p53 positivity is also characteristic of carcinoma bu t may be seen in benign-appearing urothelium, suggesting a "field effect" w ith occult molecular aberration.