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 morphologic continuum between benign and carcinomatous prostate, but its status as a neoplastic precursor remains only putative. We measured nuclear proliferative activity using MIB-1 antibody to further characterize the cell kinetics of HG-PIN and to assess its relationship to prostatic adenocarcinoma. We studied 36 specimens from randomly selected patients who underwent radical prostatectomies for prostatic adenocarcinoma. Sections of formalin-fixed, paraffin-embedded tissue pretreated by a citric acid monohydrate antigen retrieval method were immunostained with the mouse monoclonal antibody MIB-1, which detects the Ki-67 antigen in formalin-fixed tissue. The Ki-67 antigen is expressed by non-G0 proliferating cells and has been used to assess cellular proliferative activity. A maximum of either 20,400 x fields or 100 positively stained nuclei in benign glands, areas of HG-PIN, and adenocarcinoma were counted to obtain an immunohistologic proliferation index for each case. For benign prostate, HG-PIN, and adenocarcinoma, the mean positivity was 0.4 +/- 0.42 cells per field (range, 0-2), 2.5 +/- 3.79 cells per field (range, 0-16.6), and 13.8 +/- 15.05 cells per field (range, 0.25-73.66), 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 histologic categories (P < 0.01, all three comparisons). In addition, the proliferative index consistently increased along the continuum from benign to malignant. We conclude that the MIB-1 proliferative index of HG-PIN lies between that of benign and carcinomatous prostate, supporting the assertion that HG-PIN is a biologic intermediate in the multistep process of transformation into carcinoma.
Department of Pathology, Henry Ford Hospital, Detroit, Michigan 48202, USA.
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P
Tamboli
M B
MB
Amin
D S
DS
Schultz
M D
MD
Linden
J
J
Kubus
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology*; D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D002455:Cell Division; D004273:DNA, Neoplasm / Q000032:analysis; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000032:analysis*; D008297:Male; D009687:Nuclear Proteins / Q000032:analysis; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis*; D011467:Prostate / Q000737:chemistry / Q000166:cytology*; D019048:Prostatic Intraepithelial Neoplasia / Q000737:chemistry / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000473:pathology*
D000911:Antibodies, Monoclonal; D034961:Antigens, Nuclear; D004273:DNA, Neoplasm; D019394:Ki-67 Antigen; D009687:Nuclear Proteins; D018809:Proliferating Cell Nuclear Antigen