Prostate-Specific Membrane Antigen Expression in Neovasculature of Glioblastoma Multiforme

Document Type : Original Article


Department of Pathology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Glioblastoma (GBM) is the most malignant brain tumor with a poor prognosis that can be very difficult to cure, and the current treatment options have no optimal outcomes. Hence, it is essential to find new treatment modalities. Histologically, this tumor has high microvascular density that makes it desirable for vascular target agent drugs. Prostate-specific membrane antigen (PSMA) is a novel antigen with unique features that expresses in the vascular endothelium of some malignant tumors. Materials and Methods: Formalin-fixed paraffin-embedded tissues from sixty patients who underwent GBM tumor resection from 2012 to 2016 were evaluated for the expression of PSMA by immunohistochemistry. Sections were also assessed for the extent and intensity of endothelial staining in tumor microvessels and for clinicopathologic factor correlation. Results: A considerable PSMA expression level was detected in 66% of the cases, and the intensity was strong and moderate in 63%. There was no significant correlation neither between PSMA expression with tumor site, presence of necrosis, and endothelial proliferation nor with age and sex. Conclusion: The expression of PSMA in GBM, as observed in the current study, may suggest a new role of PSMA-targeted therapy and indicate more investigations focused on complementary treatment strategies that specifically target tumor vasculature.


Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 1
Purow B, Schiff D. Advances in the genetics of glioblastoma: Are we reaching critical mass? Nat Rev Neurol 2009;5:419-26.  Back to cited text no. 2
Ostrom QT, Gittleman H, Farah P, Ondracek A, Chen Y, Wolinsky Y, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006-2010. Neuro Oncol 2013;15 Suppl 2:ii1-56.  Back to cited text no. 3
Juratli TA, Schackert G, Krex D. Current status of local therapy in malignant gliomas – A clinical review of three selected approaches. Pharmacol Ther 2013;139:341-58.  Back to cited text no. 4
Carlsson SK, Brothers SP, Wahlestedt C. Emerging treatment strategies for glioblastoma multiforme. EMBO Mol Med 2014;6:1359-70.  Back to cited text no. 5
Kim WY, Lee HY. Brain angiogenesis in developmental and pathological processes: Mechanism and therapeutic intervention in brain tumors. FEBS J 2009;276:4653-64.  Back to cited text no. 6
Thorpe PE. Vascular targeting agents as cancer therapeutics. Clin Cancer Res 2004;10:415-27.  Back to cited text no. 7
Carter RE, Feldman AR, Coyle JT. Prostate-specific membrane antigen is a hydrolase with substrate and pharmacologic characteristics of a neuropeptidase. Proc Natl Acad Sci U S A 1996;93:749-53.  Back to cited text no. 8
Horoszewicz JS, Kawinski E, Murphy GP. Monoclonal antibodies to a new antigenic marker in epithelial prostatic cells and serum of prostatic cancer patients. Anticancer Res 1987;7:927-35.  Back to cited text no. 9
Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB, et al. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res 1999;59:3192-8.  Back to cited text no. 10
Liu H, Moy P, Kim S, Xia Y, Rajasekaran A, Navarro V, et al. Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium. Cancer Res 1997;57:3629-34.  Back to cited text no. 11
Milowsky MI, Nanus DM, Kostakoglu L, Sheehan CE, Vallabhajosula S, Goldsmith SJ, et al. Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol 2007;25:540-7.  Back to cited text no. 12
Morris MJ, Pandit-Taskar N, Divgi CR, Bender S, O'Donoghue JA, Nacca A, et al. Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors. Clin Cancer Res 2007;13:2707-13.  Back to cited text no. 13
Fung EK, Cheal SM, Fareedy SB, Punzalan B, Beylergil V, Amir J, et al. Targeting of radiolabeled J591 antibody to PSMA-expressing tumors: Optimization of imaging and therapy based on non-linear compartmental modeling. EJNMMI Res 2016;6:7.  Back to cited text no. 14
Bychkov A, Vutrapongwatana U, Tepmongkol S, Keelawat S. PSMA expression by microvasculature of thyroid tumors – Potential implications for PSMA theranostics. Sci Rep 2017;7:5202.  Back to cited text no. 15
Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee S Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev 2017;18:3-9.  Back to cited text no. 16
Philips A, Henshaw DL, Lamburn G, Carroll MJ. Brain tumours: Rise in glioblastoma multiforme incidence in England 1995 and #x2013;2015 suggests an adverse environmental or lifestyle factor. J Environ Public Health 2018;2018:10.  Back to cited text no. 17
Bondy ML, Scheurer ME, Malmer B, Barnholtz-Sloan JS, Davis FG, Il'yasova D, et al. Brain tumor epidemiology: Consensus from the brain tumor epidemiology consortium. Cancer 2008;113:1953-68.  Back to cited text no. 18
Homma T, Fukushima T, Vaccarella S, Yonekawa Y, Di Patre PL, Franceschi S, et alC orrelation among pathology, genotype, and patient outcomes in glioblastoma. J Neuropath Exp Neurol 2006;65:846-54.  Back to cited text no. 19
Wernicke AG, Edgar MA, Lavi E, Liu H, Salerno P, Bander NH, et al. Prostate-specific membrane antigen as a potential novel vascular target for treatment of glioblastoma multiforme. Arch Pathol Lab Med 2011;135:1486-9.  Back to cited text no. 20
Nomura N, Pastorino S, Jiang P, Lambert G, Crawford JR, Gymnopoulos M, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases. Cancer Cell Int 2014;14:26.  Back to cited text no. 21
Saffar H, Noohi M, Tavangar SM, Saffar H, Azimi S. Expression of prostate-specific membrane antigen (PSMA) in brain glioma and its correlation with tumor grade. Iran J Pathol 2018;13:45-53.  Back to cited text no. 22