P. Tamboli et al., COMPARATIVE-ANALYSIS OF THE NUCLEAR PROLIFERATIVE INDEX (KI-67) IN BENIGN PROSTATE, PROSTATIC INTRAEPITHELIAL NEOPLASIA, AND PROSTATIC-CARCINOMA, Modern pathology, 9(10), 1996, pp. 1015-1019
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.