PROSTATE-SPECIFIC MEMBRANE ANTIGEN EXPRESSION IN NORMAL AND MALIGNANTHUMAN TISSUES

Prostate-specific membrane antigen is a type LI membrane protein,vith folate hydrolase activity produced by prostatic epithelium. The expres sion of this molecule has also been documented in extraprostatic tissu es, including small bowel and brain, Tn the present study, an extensiv e immunohistochemical analysis was performed on a panel of well-charac terized normal and malignant human tissues to further define the patte rn 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 neuroendoc rine cells in the colonic crypts also exhibited PSMA immunoreactivity, All other normal tissues, including cerebral cortex and cerebellum, h ad undetectable levels of PSMA, Thirty-three of 35 primary prostate ad enocarcinomas and 7 of 8 lymph node metastases displayed tumor cell PS MA immunostaining, Eight of 18 prostate tumors metastatic to bone expr essed PSMA. All of the other nonprostatic primary tumors studied had u ndetectable PSMA levels. However, intense staining was observed in end othelial cells of capillary vessels in peritumoral and endotumoral are as of certain malignancies, including 8 of 17 renal cell carcinomas, 7 of 13 transitional cell carcinomas, and 3 of 19 colon carcinomas, Ext raprostatic PSMA expression appears to be highly restricted, Neverthel ess, its diverse anatomical distribution implies a broader functional significance than previously suspected, The decrease in PSMA immunorea ctivity noted in advanced prostate cancer suggests that expression of this molecule may be linked to the degree of tumor differentiation, Th e neoexpression of PSMA in endothelial cells of capillary beds in cert ain tumors may be related to tumor angiogenesis and suggests a potenti al mechanism for specific targeting of tumor neovasculature.