Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature

Prostate-specific membrane antigen (PSMA) is a type II integral membrane gl ycoprotein that was initially characterized by the monoclonal antibody (mAb ) 7E11. PSMA is highly expressed in prostate secretory-acinar epithelium an d prostate cancer as well as in several extraprostatic tissues. Recent evid ence suggests that PSMA is also expressed in tumor-associated neovasculatur e. We examined the immunohistochemical characteristics of 7E11 and those of four recently developed anti-PSMA mAbs (J591, J415, and Hybritech PEQ226.5 and PM2J004.5), each of which binds a distinct epitope of PSMA. Using the streptavidin-biotin method, we evaluated these mAbs in viable prostate canc er cell lines and various fresh-frozen benign and malignant tissue specimen s. In the latter, we compared the localization of the anti-PSMA mAbs to tha t of the antiendothelial cell mAb CD34. With rare exceptions, all five anti -PSMA mAbs reacted strongly with the neovasculature of a wide spectrum of m alignant neoplasms: conventional (clear cell) renal carcinoma (11 of 11 cas es), transitional cell carcinoma of the urinary bladder (6 of 6 cases), tes ticular embryonal carcinoma (1 of 1 case), colonic adenocarcinoma (5 of 5 c ases), neuroendocrine carcinoma (5 of 5 cases), glioblastoma multiforme (1 of 1 cases), malignant melanoma (5 of 5 cases), pancreatic duct carcinoma ( 4 of 4 cases), non-small cell lung carcinoma (5 of 5 cases), soft tissue sa rcoma (5 of 6 cases), breast carcinoma (5 of 6 cases), and prostatic adenoc arcinoma (2 of 12 cases). Localization of the anti-PSMA mAbs to tumor-assoc iated neovasculature was confirmed by CD34 immunohistochemistry in sequenti al tissue sections. Normal vascular endothelium in non-cancer-bearing tissu e was consistently PSMA negative. The anti-PSMA mAbs reacted with the neopl astic cells of prostatic adenocarcinoma (12 of 12 cases) but not with the n eoplastic cells of any other tumor type, including those of benign and mali gnant vascular tumors (0 of 3 hemangiomas, 0 of 1 hemangioendothelioma, and 0 of 1 angiosarcoma). The mAbs to the extracellular PSMA domain (J591, J41 5, and Hybritech PEQ226.5) bound viable prostate cancer cells (LNCaP and PC 3-PIP), whereas the mAbs to the intracellular domain (7E11 and Hybritech PM 2J004.5) did not. All five anti-PSMA mAbs reacted with fresh-Frozen benign prostate secretory-acinar epithelium (28 of 28 cases), duodenal columnar (b rush border) epithelium (11 of 11 cases), proximal renal tubular epithelium (5 of 5 cases), colonic ganglion cells (1 of 12 cases), and benign breast epithelium (8 of 8 cases). A subset of skeletal muscle cells was positive w ith 7E11 (7 of 7 cases) and negative with the other four anti-PSMA mAbs. PS MA was consistently expressed in the neovasculature of a wide variety of ma lignant neoplasms and may be an effective target for mAb-based antineovascu lature therapy.