Prostate-specific membrane antigen expression in normal and malignant human tissues

• Published in: Clinical cancer research Vol. 3; no. 1; pp. 81 - 85
• Main Authors: SILVER, D. A, PELLICER, I, FAIR, W. R, HESTON, W. D. W, CORDON-CARDO, C
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-01-1997
• Subjects: Antigens, Neoplasm - biosynthesis; Antigens, Surface; Biological and medical sciences; Carboxypeptidases - biosynthesis; Glutamate Carboxypeptidase II; Humans; Immunohistochemistry; Male; Medical sciences; Nephrology. Urinary tract diseases; Prostate - metabolism; Prostate - pathology; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Tissue Distribution; Tumors of the urinary system; Urinary tract. Prostate gland; Adenocarcinoma; Human; Immunohistochemistry; Membrane protein; Urinary system disease; Prostate disease; Tumoral tissue; Biological marker; Tumoral marker; Malignant tumor; Gene expression; Normal; In vitro; Prostate specific antigen; Neovascularization; Detection; Male genital diseases; Prostate
• ISSN: 1078-0432; 1557-3265

Prostate-specific membrane antigen is a type II membrane protein with folate hydrolase activity produced by prostatic epithelium.
The expression of this molecule has also been documented in extraprostatic tissues, including small bowel and brain. In the
present study, an extensive immunohistochemical analysis was performed on a panel of well-characterized normal and malignant
human tissues to further define the pattern of prostate-specific membrane antigen (PSMA) expression. Detectable PSMA levels
were identified in prostatic epithelium, duodenal mucosa, and a subset of proximal renal tubules. A subpopulation of neuroendocrine
cells in the colonic crypts also exhibited PSMA immunoreactivity. All other normal tissues, including cerebral cortex and
cerebellum, had undetectable levels of PSMA. Thirty-three of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases
displayed tumor cell PSMA immunostaining. Eight of 18 prostate tumors metastatic to bone expressed PSMA. All of the other
nonprostatic primary tumors studied had undetectable PSMA levels. However, intense staining was observed in endothelial cells
of capillary vessels in peritumoral and endotumoral areas of certain malignancies, including 8 of 17 renal cell carcinomas,
7 of 13 transitional cell carcinomas, and 3 of 19 colon carcinomas. Extraprostatic PSMA expression appears to be highly restricted.
Nevertheless, its diverse anatomical distribution implies a broader functional significance than previously suspected. The
decrease in PSMA immunoreactivity noted in advanced prostate cancer suggests that expression of this molecule may be linked
to the degree of tumor differentiation. The neoexpression of PSMA in endothelial cells of capillary beds in certain tumors
may be related to tumor angiogenesis and suggests a potential mechanism for specific targeting of tumor neovasculature.