Ali Serdar OĞUZOĞLU, Nilgün ŞENOL, Hasan YASAN, Ramazan Oğuz YÜCEER, Cengiz GAZELOĞLU, İbrahim Metin ÇİRİŞ

GLİAL TÜMÖR TEDAVİSİNDE TAMAMLAYICI HEDEF TEDAVİ: PROSTAT SPESİFİK MEMBRAN ANTİJEN (PSMA)

Amaç Gliomalar farklı dereceleri ile en sık karşılaşılan primer beyin tümörleridir. Özellikle yüksek dereceli olanlarda tümör anjiogenezi hem ana komponenetlerden biri, hem de prognoz açısından değerli bir belirleyicidir. Bu çalışmada, farklı hedef tedavileri belirleyebilmek için immunohistokimyasal metod ile glial tümörlerde prostat spesifik membran antijeni (PSMA) salınımını değerlendirmeyi amaçladık. Gereç ve Yöntem Derece II (n=22), Derece III (n=19) ve Derece IV (n=52) glial tümörlü 93 hastadan alınan örneklerde PSMA antikorları immunohistokimyasal metod ile incelendi. Tümör dokusundaki PSMA boyanma yoğunluğu ve tümör epitelleri incelendi. Tümör epitelinde tümör ve tümör-dışı dokuda PSMA salınımına göre vasküler salınım ve yoğunluk skoru analiz edildi. Bulgular Yüksek dereceli gliomalarda, vasküler PSMA boyanma yüzdesi ve vasküler yoğunluk skoru düşük derecelilere göre anlamlı olarak daha yüksek (p<0,005) bulundu. Tümör epitelinde vasküler PSMA boyanma yüzdesinde (p<0,05) düşük derecelilerde anlamlı bir yükseklik (p<0,05) olmasına rağmen, yüksek derecelilerde görülen vasküler yoğunluk yüzdesindeki yükseklik anlamlı değildi. Sonuç Yüksek dereceli glial tümörlerde neovaskülarizasyonun fazla olması ile PSMA ekspresyon yüzdesi ve yoğunluğunun anlamlı şekilde yüksek bulunması bu tümör grubunda PSMA’ne yönelik tedavi edici ajanların etkili olabileceğini göstermektedir.

Anahtar Kelimeler:

glial tümör, prostat-spesifik membran, anjiogenez, antigen

PROSTATE-SPECIFIC MEMBRANE ANTIGEN (PSMA) FOR A COMPLEMENTARY TARGET THERAPY IN GLIAL TUMORS

Objective Gliomas are the most common primary brain tumors with different grades. Especially in the high grade gliomas tumor angiogenesis is an essential component, and a valuable marker for the prognosis. In this stuıdy we aimed to evaluate the expression of prostate specific membrane antigen (PSMA) in glial tumors by immunochemistry method to determine different targeted therapies. Material and Methods Overall 93 patients’ specimens, including Grade II (n=22), Grade III (n=19), Grade IV (n=52) glial tumors, were evaluated for PSMA-antibody via immunohistochemical method. PSMA staining intensities in tumor tissue and tumor epithelium were analyzed. Vascular expression in tumoral and extratumoral stroma, and intensity score, according to PSMA expression, in tumoral epithelium were analyzed. Results In high grade gliomas, vascular PSMA staining percentage and vascular intensity score were significantly higher than low grade (p<0.05). In the epithelium of the tumors, although a significant increase was observed in vascular PSMA staining percentage (p<0.05) of low grade tumors, the increase in vascular intensity score of high grade tumors was not significant. Conclusion Significant increase in PSMA staining percentage and vascular intensity score of tumor stroma in high grade gliomas due to more neovascularisation, demonstrates that therapeutic agents can be effective in this group of tumors.

Keywords:

glial tumor, prostate-spesific membrane, angiogenesis, antigen,

PDF

___

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.
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.
J.D. Mangadlao, X. Wang, C. McCleese, M. Escamilla, G. Ramamurthy, Z. Wang, M. Govande, J.P. Basilion, C. Burda, Prostate specific membrane antigen targeted gold nanoparticles for theranostics of prostate cancer, ACS Nano 12 (2018) 3714–3725.
Ni J, Miao T, Su M, KhanNU, Ju X, Chen H, Liu F, Han L. PSMA-targeted nonaparticles for spesific penetration of blood-brain tumor barrier and combined therapy of brain metastases. J of Controlled Release 2021;329:934-947.
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.
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).
Grau SJ, Trillsch F, Luttichau Iv, et al. Lymphatic phenotype in tumor vessels in malignant gliomas. Neuropathology and Applied Neurobiology. 2008;34:675–9.
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(1):45-53.
Wernicke AG, Varma S, Greenwood EA et al Prostate‐specific membrane antigen expression in tumor‐associated vasculature of breast cancers. Apmis 2014;122(6):482-9.
Wernicke AG, Kim S, Liu H, Bander NH, Pirog EC Prostate-specific membrane antigen (PSMA) expression in the neovasculature of gynecologic malignancies: implications for PSMA-targeted therapy. Immunohistochemistry & Molecular Morphology 2017;25(4):271-6.
Milowsky MI, Nanus DM, Kostakoglu L, Sheehan CE, Vallabhajosula S, Goldsmith SJ, Ross JS, Bander NH (2007) Vascular targeted therapy with anti-prostate-specific membrane antigen monoclonal antibody J591 in advanced solid tumors. J Clin Oncol 25:540–547.
Karyagar SS. PSMA- positive secondary tumors in ⁶⁸Ga PSMA PET/CT imaging in patients with prostate cancer. Eur Arch Med Res 2020;36(4):246-50.
Matsuda M, Ishikawa E, Yamamoto T, Hatano K, Joraku A, Lizumi Y, Masuda Y, Nishiyama H, Matsumara A. Potential use of prostate spesific membrane antigen (PSMA) for detecting the tumor neovasculature of brain tumors by PET imaging with ⁸⁹Zr-Df-IAB2M anti-PSMA minibody. J of Neuro-Oncology 2018;138:581-589.
Vargas J, Perez FG, Gomez E, Pitalua Q, Ornelas M, Ignacio E, et al. Histopathologic correlation with ⁶⁸Ga PSMA PET/CT in nonprostate tumors. Journal of Nuclear Medicine 2020;61 (Suppl 1):472.
Özülker F. Assessment of physiological distribution and normal variants of 68Ga PSMA-I&T PET/CT. Eur Arch Med Res 2018;34:235-42.
Demirci E, Sahin OE, Ocak M, Akovali B, Nematyazar J, Kabasakal L. Normal distribution pattern and physiological variants of 68GaPSMA-11 PET/CT imaging. Nucl Med Commun 2016;37:1169-79.
Holzgreve A, Biczok A, Ruf VC, Liesche-Starnecker F, Steiger K et al. PSMA expression in glioblastoma as a basis for theranostic approaches: a retrospective, correlation panel study including immunohistochemistry, clinical parameters and PET imaging. Front Oncol 2021;11:646387.