Immunohistochemical detection of cysteine‐rich secretory protein 3 in tissue and in serum from men with cancer or benign enlargement of the prostate gland

Abstract

Recently, the gene for cysteine-rich secretory protein 3 (CRISP-3) was reported to be highly upregulated in prostate cancer (PCa) compared to benign prostatic tissue. The current aims were to investigate diagnostic use of tissue expression and immunodetection in serum of CRISP-3 for detection or monitoring of PCa. Radical prostatectomy specimens and tissue microarrays from transurethral resections and metastases were analyzed for CRISP-3 and PSA by immunohistochemistry. CRISP-3 in tissue homogenates and in serum was measured by an in-house ELISA and PSA by a commercially available immunoassay. Immunostaining for CRISP-3 in benign prostatic epithelium was generally weak or not detectable. Specific and strong immunostaining was found in a major proportion of cells in high-grade prostatic-intraepithelial-neoplasia (HG-PIN,12/17 patients), in most primary tumors (111/115), and in lymph node (11/15) and bone (12/15) metastases. CRISP-3 immunostaining intensity was regularly strong in areas of Gleason grades 4/5, where PSA-immunoreaction was less intense. Serum levels of CRISP-3 were not different in patients with PCa (n=152) compared to men with BPH (n=81). There was a very weak co-variation between levels of CRISP-3 versus PSA in serum from PCa patients (P<0.05). After orchiectomy, levels of CRISP-3 in serum decreased in median with 11% compared to a 97% median decrease of PSA in serum from 15/20 patients with advanced PCa. Strong immunostaining for CRISP-3 is common in HG-PIN and preserved in most PCa specimens, which warrant further immunohistochemical studies of CRISP-3 in PCa. Serum levels of CRISP-3 do not primarily reflect PCa.