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Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. 1997

M F Darson, and A Pacelli, and P Roche, and H G Rittenhouse, and R L Wolfert, and C Y Young, and G G Klee, and D J Tindall, and D G Bostwick
Department of Urology, Mayo Clinic, Rochester, MN 35905, USA.

OBJECTIVE We describe the expression of a potentially new tumor marker, human glandular kallikrein 2 (hK2), that may be useful as an adjunct to prostate-specific antigen (PSA) in the diagnosis and monitoring of prostate cancer. METHODS We evaluated 257 radical prostatectomy specimens removed at the Mayo Clinic with pathologic Stage 12 adenocarcinoma to compare the cytoplasmic expression of hK2, PSA, and prostatic acid phosphatase (PAP) in benign tissue, high-grade prostatic intraepithelial neoplasia (PIN), and adenocarcinoma. Two monoclonal antibodies, hK2-A523 and hK2-G586, specific for hK2 were used, as well as antibodies against PSA (PSM-773) and PAP (polyclonal). RESULTS Intense epithelial cytoplasmic immunoreactivity was observed in every case for hK2-A523, hK2-G586, PSA, and PAP (100% of cases, respectively). The intensity and extent of hK2 expression for both antibodies were greater in cancer than high-grade PIN; furthermore, high-grade PIN was greater than benign epithelium. Cases of Gleason primary grade 4 and 5 cancer showed hK2 staining in almost every cell, whereas there was greater heterogeneity of staining in lower grades of cancer. In marked contrast to hK2, PSA and PAP immunoreactivity was most intense in benign epithelium and stained to a lesser extent in PIN and carcinoma. The number of immunoreactive cells for hK2 and PSA was not predictive of cancer recurrence. CONCLUSIONS hK2 was expressed in every cancer, and the expression incrementally increased from benign epithelium to high-grade PIN and adenocarcinoma. PSA and PAP displayed inverse immunoreactivity compared with hK2. The expression of hK2 and PSA was not predictive of cancer recurrence in patients with Stage T2 carcinoma. Expression of hK2 indicates that this kallikrein antigen is both prostate localized and tumor associated. Tissue expression of hK2 appears to be regulated independently of PSA and PAP. Further studies are needed to determine whether tissue immunoreactivity of hK2 will prove clinically useful in the diagnosis and monitoring of prostate cancer.

UI MeSH Term Description Entries
D007610 Kallikreins Proteolytic enzymes from the serine endopeptidase family found in normal blood and urine. Specifically, Kallikreins are potent vasodilators and hypotensives and increase vascular permeability and affect smooth muscle. They act as infertility agents in men. Three forms are recognized, PLASMA KALLIKREIN (EC 3.4.21.34), TISSUE KALLIKREIN (EC 3.4.21.35), and PROSTATE-SPECIFIC ANTIGEN (EC 3.4.21.77). Kallikrein,Kininogenase,Callicrein,Dilminal,Kallidinogenase,Kalliginogenase,Kallikrein A,Kallikrein B',Kallikrein Light Chain,Kinin-Forming Enzyme,Padutin,alpha-Kallikrein,beta-Kallikrein,beta-Kallikrein B,Enzyme, Kinin-Forming,Kinin Forming Enzyme,Light Chain, Kallikrein,alpha Kallikrein,beta Kallikrein,beta Kallikrein B
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D011467 Prostate A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM. Prostates
D011471 Prostatic Neoplasms Tumors or cancer of the PROSTATE. Cancer of Prostate,Prostate Cancer,Cancer of the Prostate,Neoplasms, Prostate,Neoplasms, Prostatic,Prostate Neoplasms,Prostatic Cancer,Cancer, Prostate,Cancer, Prostatic,Cancers, Prostate,Cancers, Prostatic,Neoplasm, Prostate,Neoplasm, Prostatic,Prostate Cancers,Prostate Neoplasm,Prostatic Cancers,Prostatic Neoplasm
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000135 Acid Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.2. Acid beta-Glycerophosphatase,Acid beta Glycerophosphatase
D000230 Adenocarcinoma A malignant epithelial tumor with a glandular organization. Adenocarcinoma, Basal Cell,Adenocarcinoma, Granular Cell,Adenocarcinoma, Oxyphilic,Adenocarcinoma, Tubular,Adenoma, Malignant,Carcinoma, Cribriform,Carcinoma, Granular Cell,Carcinoma, Tubular,Adenocarcinomas,Adenocarcinomas, Basal Cell,Adenocarcinomas, Granular Cell,Adenocarcinomas, Oxyphilic,Adenocarcinomas, Tubular,Adenomas, Malignant,Basal Cell Adenocarcinoma,Basal Cell Adenocarcinomas,Carcinomas, Cribriform,Carcinomas, Granular Cell,Carcinomas, Tubular,Cribriform Carcinoma,Cribriform Carcinomas,Granular Cell Adenocarcinoma,Granular Cell Adenocarcinomas,Granular Cell Carcinoma,Granular Cell Carcinomas,Malignant Adenoma,Malignant Adenomas,Oxyphilic Adenocarcinoma,Oxyphilic Adenocarcinomas,Tubular Adenocarcinoma,Tubular Adenocarcinomas,Tubular Carcinoma,Tubular Carcinomas
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly

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