Document Type : Original Research
Authors
1 Dept. of Pathology, Shariati Hospital, Tehran University of Medical Sciences, Iran
2 Dept. of Pathology, Imam Hospital Complex, Tehran University of Medical Sciences, Iran
Abstract
Background & Objective Angiogenesis is an essential component of tumor growth. Expression of PSMA on the neo-vasculature of many solid tumors, including glioblastoma multi-form, has been determined. The pattern of expression suggests that PSMA may play a functional role in angiogenesis.
Methods: expression of PSMA in different grades of brain glioma was evaluated by the immunohistochemistry method to determine the probable usefulness of anti-PSMA antibody as complementary target therapy in different grades of glioma.
Results: Overall, 72 cases of low (grade I and II) and high (grade III and IV) grade gliomas were evaluated for expression of PSMA. Positive PSMA staining was observed in 12 (33.3%) of high grade and 3 (8.3%) of low grade gliomas. Although, high grade tumors more commonly had positive result for PSMA (P value=0.009), the intensity of staining was significantly stronger in low-grade tumors (P value=0.009).
Conclusion: Expression of PSMA in different grades of glioma might provide a basis for further investigations focusing on selective target therapy in combination with the current standard care in all glioma grades, to improve treatment efficacy.
Keywords
- Carlsson SK, Brothers SP, Wahlestedt C. Enmerging treatment strategies for glioblastoma multiforme. EMBO Molecular Medicine. 2014;6(11):1359-70.
- Nomura N, Pastorino S, Jiang P, et al. Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastasis. Caner Cell International. 2014;14:26.
- Patel MA, Kim JE, Ruzevick J,et al. The Future of Glioblastoma Therapy: Synergism of Standard of Care and Immunotherapy Cancers. 2014;6:1953-85.
- DeAngelis L. Brain tumors. N England J Med. 2001;344:114-23.
- Parsa A, Waldron J, Panner A, et al. Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med. 2006;13:84-8.
- Wernicke AG, Edgar MA, Lavi E, et al. Prostate Specific Membrane Antigen as a potential Novel Vascular Target for Treatment of Glioblastoma Multiforme. Aarchives of Pathology and Laboratory Medicine. 2011;135:1486-9.
- Shi W, Siemann D. Targeting the tumor vasculature: enhancing antitumor efficacy through combination treatment with ZD6126 and ZD6474. In Vivo. 2005;19(6):1045-50.
- Burkhardt J, Hofstetter C, Santillan A, et al. Orthotopic glioblastoma stem-like cell xenograft model i mice to evaluateintra-arterial delivery of bevacizumab:from bedside to bench. J Clin Neurosci. 2012;19:1568-72.
- Chen K, Huang Y-h, Chen J-l. Understanding and targeting cancer stem cells: therapeutic implications and challenges. Acta Pharmacologica Sinica. 2013;34:732-40.
- pasqualini R, Arap W, McDonald D. Probing the stractural and molecular diversity f tumor vasculature. Trends Molecular Medicine. 2002;8(12):563-71.
- Plate K, Risau W. Angigenesis in malignant gliomas. Glia. 1995;15(3):339-47.
- Scappaticci F. Mechanisms and future directions for angiogenesis based cancer therapies. Journal of Clinical Oncology. 2002;20(18):3906-27.
- Chang S, Reuter V, Heston W, Gaudin P. Metastatic Renal Cell Carcinoma neovasulature express Prostatic-Specific membrane antigen. Urology. 2001;57(4):801-5.
- Gopalakrishnapillai A, Sonali PB, Jason JC, et al. Assossiation of Prostate-specific membrane antigen with caveolin-1 and its caveola-dependent internalization in microvascular endothelial cells:implications for targeting to tumor vasculture Microvascular research. 2006;72:45-61.
- Grau SJ, Trillsch F, Luttichau Iv, et al. Lymphatic phenotype in tumor vessels in malignant gliomas. Neuropathology and Applied Neurobiology. 2008;34:675-9.
- Bander N, Milowsky M, Nanus D, et al. Phase I trial of 177 lutetium-labeled J591, a monoclonal antibody to prostate-membrane antigen , in patients with androgen independent prostate cancer. Journal of Clinical Oncology. 2005;23(13):4591-601.
- Liu H, Moy P, Kim S, al e. Monoclonal antibodies to the extracellular domain of prostate-specific membrane antigen also react with tumor vascular endothelium Cancer Research. 1997;57(17):3629-34.
- Mhawech-Fauceglia P, Zhang S, Terraccino L,et al. prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: an immunohistochemical study using multiple tumor tissue micoarray technique Histopathology. 2007;50(4):472-83.
- chang SS, Reuter VE, Heston WDW,et al. Five different Anti-Prostate- Specific Membrane Antigen (PSMA) antibodies confirm PSMA expression in tumor associated neovasculature. Cancer Research. 1999;59:3192.
- Akhtar NH, Pail O, Saran A,et al. Prostate-Spaecific Membrane Antigen-Based Therapeutics. Advances in Urology. 2012;Article ID973820(doi:10.1155/2012/973820).
- Troyler J, Beckett M, Jr GW. Detection and characterization of the prostate-specific membrane antigen(PSMA) in tissue extracts and body fluid,". International journal of Cancer. 1995;26(5):552-8.
- Tsui P, Rubenstein N, Guinan P. Correlation between PSMA and VEGF expression as markers for LNCap tumor angiogenesis. Journal of Biomedicine and Biotechnology. 2005;3:287-90.
- Milowsky M, Nanus D, Kostakoglu L,et al. Vn advanced solid tumorsascular targeted therapy with anti Prostate-specific membrane antigen monoclonal antibody J591 i. Journal of Clinical Oncology. 2007;25(5):540-7.
- Morris M, Pandit-Taskar N, Divgi C,et al. Phase I evaluation of J591 as a vascular targeting agent in progressive solid tumors. Clinical Cancer Research. 2007;13(9):2707-13.
- Haffner M, Kronberger I, Ross J, et al. Prostate-Specific Membrane Antigen expression in the neovasulature of gastric and colorectal cancers. Human Pathology. 2009;40:1754-62.
- Sacha P, Zamecnik J, Barinka C, et al. Expression of glutamate carboxypeptidase II in human brain. NeuroScience. 2007;144:1361-72.
- Kirsch M, Schackert G, Black P. Anti-angiogenic treatment strategies for malignant brain tumours. Journal of Neurooncology. 2000;50:149-63.
- Roskoski R. Sanitinib: a VEGF and PDGF receptor protein kinase and angiogenesis inhibitor. Biochem Biophys Res Commun. 2007;356:323-8.
- Takano S, Kamiyama H, Tsuboi K, Matsumura A. Angiogenesis and angiotherapy for malignant gliomas. Brain Tumor Pathology. 2004;21:69-73.
- Grau S, Trillsch F, Herms J, et al. Expression of VEGFR3in glioma endothelium correlates with tumour grade. Journal of Neurooncology. 2007;82:141-50.
- Jenny B, Harrison J, Baetens D, et al. Expression and localization of VEGF-C and VEGFR-3 in glioblastomas and haemangioblastomas. Journal of pthology. 2006;209:34-43.
- Ferrara N, Hillan K, Novotny W. Bevacizumab(Avastin), a humanized anti-VEGF monoclonal antibody for cancer therapy. Biochem Biophys Res Commun. 2005;333:328-35.
- Groot Jd, Fuller G, Kumar A, Piao Y, Eterovic K, Ji Y, et al. Tumor invasion after treatment of glioblastoma with bevacizumab:radiographic and pathologic correlation in humans and mice. Neuro-Oncol. 2010;12:233-42.
- Brastianos P, Bachelor T. VEGF inhibitors in brain tumors. Clin Adv Hematol Oncol. 2009;7:753-60.
- Carbonell W, Ansorge O, Sibson N, Muschel R. The vascular basement membrane as "soil" in brain metastasis. Plos One. 2009;4:e5857.
- Jain R, diTomaso E, Duda D,et al. Angiogenesis in brain tumors. Nat Rev Neurosci. 2007;8:610-22.
- Leenders W, Kusters B, Verrijp K, et al. Antiangiogenic therapy of cerebral melanoma metstases results in sustained tumor progression via vessel co-option. Clinical Cancer Research. 2004;10:6222-30.
- Paez-Ribes M, Allen E, Hudock J, Takeda T, et al. Antiangiogenic therapy elicits malignant progression of tumours to increased local invasion and distant metastasis. Cancer Cell. 2009;15:220-31.
- Grant C, Caromile L, Ho V,et al. Prostate specific membrane antigen(PSMA) regulates angiogenesis independently of VEGF during ocular veovascularization. Plos One. 2012;7:e41285.