Objectives. To characterize the immunohistochemical staining (IHS) of precursor forms of prostate-specific antigen (pro-PSA) forms in prostate cancer, high-grade prostatic intraepithelial neoplasia (HGPIN), and benign tissue from the peripheral and transition zones. Pro-PSA have previously been shown to be more concentrated in prostate cancer tissue extracts than in benign tissue. Methods. Prostate needle biopsies showing HGPIN (22 sections, 11 patients) and adenocarcinoma (30 sections, 21 patients) and 17 radical prostatectomy and 3 open prostatectomy specimens were identified from the surgical pathology files of Johns Hopkins Hospital. IHS was performed on formalin-fixed, paraffin-embedded sections using one monoclonal antibody (mAB) against pro-PSA with a truncated pro-leader peptide containing two amino acids, [-2]pPSA, and a second mAB against native pro-PSA ([-5/-7]pPSA). Results. The mABs were specific for both benign and malignant prostatic glandular tissue and did not stain stromal, vascular, or colonic tissue when present in the specimens. All sections with HGPIN and/or adenocarcinoma showed staining with both mABs. HGPIN was strongly positive in most cases (66.1%). The native pro-PSA mAB showed little differential between cancer and benign glands, and the mAB to the truncated [-2]pPSA stained cancer tissue more strongly than benign tissue. Benign atrophic glands often showed negative or weak/patchy staining. No difference was found in the staining pattern between benign glands in the peripheral zone and transition zone. Conclusions. This study is the first to demonstrate that mABs to pro-PSA can be used as specific IHS for benign and malignant prostatic tissue. [-2]pPSA appears to be preferentially more concentrated in cancer tissue than in benign glands, correlating with previous tissue extract studies. Unlike previous studies with PSA staining, the IHS for pro-PSA remained uniform among the different tumor grades. Therefore, pro-PSA may be a useful marker in differentiating high-grade prostate adenocarcinoma from other non-prostate carcinomas.
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