Öz
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
Destekleyen Kurum
Süleyman Demirel Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi
Proje Numarası
TSG 2020-8134
Teşekkür
-
Kaynakça
- 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.
Öz
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.
Anahtar Kelimeler
Proje Numarası
TSG 2020-8134
Kaynakça
- 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.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Cerrahi |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Proje Numarası | TSG 2020-8134 |
| Yayımlanma Tarihi | 1 Mart 2022 |
| Gönderilme Tarihi | 1 Şubat 2022 |
| Kabul Tarihi | 7 Şubat 2022 |
| Yayımlandığı Sayı | Yıl 2022 Cilt: 29 Sayı: 1 |
Süleyman Demirel Üniversitesi Tıp Fakültesi Dergisi/Medical Journal of Süleyman Demirel University is licensed under Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International.