Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme

Abstract

Context: Prostate-specific membrane antigen (PSMA) is expressed in endothelium of vessels in malignant solid tumors but not in normal vessels.

Objective: To examine whether neovasculature of glioblastoma multiforme (GBM) expresses PSMA. Design.-After institutional review board approval at Memorial Sloan-Kettering Cancer Center, formalin-fixed paraffin-embedded tissue from 32 patients who underwent a maximally safe neurologic resection during 2004 to 2005 for GBM (World Health Organization criteria) was obtained. We performed immunohistochemical staining on the vessels of the GBM specimens for PSMA expression in tumor endothelium. The tissue samples were also stained for CD31 to verify that the PSMA was staining tumor vessels. The PSMA percent staining was scored: less than 5%, 6% to 25%, 26% to 50%, 51% to 75%, and 76% to 100%. Staining intensity was ranked as follows: 0 (none), 1+ (faint), 2+ (moderately-intense), and 3+ (maximum-intensity).

Results: Immunohistochemical staining on the vessels of 32 paraffin-embedded GBM specimens revealed that all 32 (100%) specimens exhibited staining for PSMA to a variable extent. Of these, 22 of 32 specimens (69%) had more than 51% vascular staining for PSMA. The intensity of staining was 2+ to 3+ in most of the specimens (29 of 32; 91%).

Conclusions: Prostate-specific membrane antigen is expressed in the vasculature of GBM vessels, thus rendering a potential novel therapeutic vascular target. A clinical trial with a cytotoxin-conjugated antibody to PSMA is planned.