Expression Of Prostate Specific Membrane Antigen In The Neo-Vasculature Of Non-Prostate Cancers

3110 Background: Prostate specific membrane antigen (PSMA), a transmembrane folate hydrolase consisting of 750 amino acids, has been consistently detected in normal and hyperplastic prostate tissues, in pre-cancerous lesions and prostate cancer (PCa) using immunohistochemistry and other techniques. The expression of PSMA in Non-PCa is currently being pursued as a target for diagnostic imaging and anti-cancer antibody therapeutics. Methods: PSMA expression was measured on a series of fresh frozen and formalin-fixed paraffin embedded non-PCA malignancies by transcriptional profiling (TP) using cDNA microarrays on nylon membranes, RT-PCR (Taqman), in situ hybridization (ISH), western blotting, dual co-localization immunofluorescence (IF) and immunohistochemistry (IHC) both before and after laser capture microdissection (LCM) using both internal domain (7E11) and external domain (MLN591) antibodies. Results: PSMA mRNA expression was localized to the neo-vasculature in 55% of a series of breast, colon, lung and ovarian cancers using an S-35 labeled probe and ISH. PSMA mRNA expression was localized to the endothelium of the tumor vessels after microdissection using Taqman™ RT-PCR . 40% of the same carcinomas were positive for PSMA immunoreactivity of the tumor vasculature by IHC on frozen sections with the MLN591 antibodyDual IF studies using the MLN591 antibody and anti-CD31 (PECAM-1) localized PSMA expression to the endothelium of neo-vasculature in carcinomas of the breast, colon, lung and ovary, in Wilm's tumors and neuroblastomas. Using the 7E11 antibody on paraffin sections, PSMA staining was observed in 9/10 clear cell renal cell carcinomas, 7/10 infiltrating ductal breast cancers, 6/10 invasive colorectal cancers and 4/10 non-small cell lung cancers. Conclusions: PSMA expression is regularly associated with the neo-vasculature of many non-PCas and co-localizes with endothelial cell markers. Further studies of PSMA in non-PCa as a target for both diagnostic imaging and anti-cancer antibody-based therapies appear warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc. Millennium Pharmaceuticals, Inc.