COMPARATIVE-ANALYSIS OF THE NUCLEAR PROLIFERATIVE INDEX (KI-67) IN BENIGN PROSTATE, PROSTATIC INTRAEPITHELIAL NEOPLASIA, AND PROSTATIC-CARCINOMA

High-grade prostatic intraepithelial neoplasia (HG-PIN) lies in the mo rphologic continuum between benign and carcinomatous prostate, but its status as a neoplastic precursor remains only putative. We measured n uclear proliferative activity using MIB-1 antibody to further characte rize the cell kinetics of HG-PIN and to assess its relationship to pro static adenocarcinoma We studied 36 specimens from randomly selected p atients who underwent radical prostatectomies for prostatic adenocarci noma Sections of formalin-fixed, paraffin-embedded tissue pretreated b y a citric acid monohydrate antigen retrieval method were immunostaine d with the mouse monoclonal antibody MIB-1, which detects the Ki-67 an tigen in formalin-fixed tissue, The Ki-67 antigen is expressed by non- G, proliferating cells and has been used to assess cellular proliferat ive activity. A maximum of either 20 400 x fields or 100 positively st ained nuclei in benign glands, areas of HG-PIN, and adenocarcinoma wer e counted to obtain an immunohistologic proliferation index for each c ase. For benign prostate, HG-PIN, and adenocarcinoma, the mean positiv ity was 0.4 +/- 0.42 cells per held (range, 0-2), 2.5 +/- 3.79 cells p er held (range, 0-16.6), and 13.8 +/- 15.05 cells per held (range, 0.2 5-73.66), respectively. Using a Kruskall-Wallis analysis of variance ( chi(2) = 58, P < 0.05) and the t test for dependent samples, we found that the mean Ki-67 antigen expression significantly differs between h istologic categories (P < 0.01, all three comparisons). In addition, t he proliferative index consistently increased along the continuum from benign to malignant, We conclude that the MIB-1 proliferative index o f HG-PIN lies between that of benign and carcinomatous prostate, suppo rting the assertion that HG-PIN is a biologic intermediate in the mult istep process of transformation into carcinoma.