EVALUATION OF IMMUNOHISTOCHEMICAL NEOVASCULAR PSMA AND CD34 EXPRESSIONS IN THYROID TUMORS

Year 2023, , 79 - 88, 14.03.2023

Mehmet Kıran , İbrahim Metin Çiriş

https://doi.org/10.17343/sdutfd.1172871

Abstract

Objective
The aim of this study was to investigate the place
of Prostate Specific Membrane Antigen (PSMA)
expression in differential diagnosis and its effect on
prognosis in thyroid tumors.
Material and Method
Immunohistochemical PSMA and CD34 were applied
to paraffin blocks of 95 patients diagnosed with
different histological types of thyroid cancer. The
percentage of vascular expression in the tumoral and
extratumoral stroma and the density score in the tumor
epithelium were evaluated and grouped according to
PSMA expression level. Final PSMA expression was
determined by multiplying intensity and percentage
points.
An increase in expression was observed with PSMA
in areas with neovascularization in thyroid tumors. No
vascular staining was detected with PSMA in nonneoplastic
thyroid tissue. No increase in expression
was seen in Non-invasive folicular thyroid neoplasm
with papillary like nuclear features (NIFTP) cases
compared to aggressive tumors
Conclusion
It was determined that increased PSMA expression
was associated with poor prognosis, and it was found
that it can be used to differentiate NIFTP cases from
other tumors.

Keywords

Neovascular, PSMA Expression, Thyroid Cancer

TİROİD TÜMÖRLERİNDE İMMÜNOHİSTOKİMYASAL OLARAK NEOVASKÜLER PSMA VE CD34 EKSPRESYONLARININ DEĞERLENDİRİLMESİ

Abstract

Amaç
Bu çalışmanın amacı tiroid tümörlerinde Prostat Spesifik
Membran Antijen (PSMA) ekspresyonunun ayrıcı
tanıdaki yeri ve prognoz üzerine etkisinin araştırılmasıdır.
Gereç ve Yöntem
Farklı histolojik tipteki 95 tiroid kanseri tanısı alan hastaların
parafin bloklarına immünohistokimyasal PSMA
ve CD34 uygulandı. Tümöral ve ekstratümoral stromadaki
vasküler ekspresyon yüzdesi ve tümör epitelindeki
yoğunluk skoru değerlendirildi ve PSMA ekspresyon
düzeyine göre gruplara ayrıldı. Nihai PSMA
ifadesi, yoğunluk ve yüzde puanları çarpılarak belirlendi.
Bulgular
Tiroid tümörlerinde yeni damar oluşumu olan alanlarda
PSMA ile ekspresyon artışı izlendi. Non-neoplastik
tiroid dokusunda PSMA ile vasküler boyanma saptanmadı.
Papiller Benzeri Nükleer Özellikler Gösteren
Noninvaziv Foliküler Neoplazi (NİFTP) vakalarında
agresif tümörlere göre karşılaştırıldığında ekspresyon
artışı görülmedi
Sonuç
PSMA ekspresyon artışının kötü prognozla ilişkili olduğu
saptandı ve NİFTP vakalarının diğer tümörler ile
ayrımında kullanılabileceği yönünde bulgular saptandı

Keywords

Neovaskülarizasyon, PSMA ekspresyonu, Tiroid Karsinomu

References

• 1. DeLellis RA, Lloyd RV, Heitz PU, Eng C. Pathology and Genetics of Tumours of Endocrine Organs. 3rd Edition Volume 8. Lyon: IARC Press; 2004.
• 2. Rosai J, Ackerman LV. Rosai and Ackerman’s Surgical Pathology. 10th Edition, New York: Elsevier; 2011.
• 3. Vural P. Fizyolojik ve Patolojik Anjiogenezde Vasküler Endotelyal Growth Faktörün Rolü. Türk Klinik Biyokimya Derg. 2018;16(1); 53-62
• 4. Crowther M, Brown NJ, Bishop ET, Lewis CE. Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors. J Leukoc Biol. 2001 Oct;70(4):478-90. PMID: 11590184.
• 5. Rosai J. Rosai and Ackerman's Surgical Pathology e-book 1st Ed ISBN: 9788131229842 Elsevier; 2011.
• 6. Kerbel RS. Tumor angiogenesis. N Engl J Med. 2008 May 8;358(19):2039-49. doi: 10.1056/NEJMra0706596. PMID: 18463380; PMCID: PMC4542009.
• 7. Rinker-Schaeffer CW, Hawkins AL, Su SL, Israeli RS, Griffin CA, Isaacs JT, et al. Localization and physical mapping of the prostate-specific membrane antigen (PSM) gene to human chromosome 11. Genomics. 1995;30(1):105-8.
• 8. Kawakami M, Nakayama J. Enhanced expression of prostate- specific membrane antigen gene in prostate cancer as revealed by in situ hybridization. Cancer research. 1997;57(12):2321-4.
• 9. Tsui P, Rubenstein M, Guinan P. Correlation between PSMA and VEGF expression as markers for LNCaP tumor angiogenesis. Journal of biomedicine & biotechnology. 2005;2005(3):287-90.
• 10. Chang SS, Reuter VE, Heston WD, Bander NH, Grauer LS, Gaudin PB. Five different anti-prostate-specific membrane antigen (PSMA) antibodies confirm PSMA expression in tumor-associated neovasculature. Cancer Res. 1999 Jul 1;59(13):3192-8. PMID: 10397265.
• 11. Morikawa S, Baluk P, Kaidoh T, Haskell A, Jain RK, McDonald DM. Abnormalities in pericytes on blood vessels and endothelial sprouts in tumors. The American journal of pathology. 2002;160(3):985-1000.
• 12. Silver DA, Pellicer I, Fair WR, Heston WD, Cordon-Cardo C. Prostate-specific membrane antigen expression in normal and malignant human tissues. Clinical cancer research : an official journal of the American Association for Cancer Research. 1997;3(1):81-5.
• 13. Gong MC, Chang SS, Sadelain M, Bander NH, Heston WD. Prostate-specific membrane antigen (PSMA)-specific monoclonal antibodies in the treatment of prostate and other cancers. Cancer Metastasis Rev. 1999;18(4):483-90. doi: 10.1023/a:1006308826967. PMID: 10855791.
• 14. Wernicke AG, Varma S, Greenwood EA, Christos PJ, Chao KS, Liu H, et al. Prostate-specific membrane antigen expression in tumor-associated vasculature of breast cancers. APMIS : acta pathologica, microbiologica, et immunologica Scandinavica. 2014;122(6):482-9.
• 15. 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. Applied immunohistochemistry & molecular morphology : AIMM. 2017;25(4):271-6.
• 16. Achen MG, Stacker SA. Tumor lymphangiogenesis and metastatic spread-new players begin to emerge. Int J Cancer. 2006;119(8):1755-60. doi: 10.1002/ijc.21899. PMID:16557570.
• 17. Wong R, Farrell SG, Grossmann M. Thyroid nodules: diagnosis and management. Med J Aust. 2018 Jul 16;209(2):92-98. doi: 10.5694/mja17.01204. PMID: 29996756.
• 18. O'Keefe DS, Bacich DJ, Huang SS, Heston WDW. A Perspective on the Evolving Story of PSMA Biology, PSMA-Based Imaging, and Endoradiotherapeutic Strategies. J Nucl Med. 2018 Jul;59(7):1007-1013. doi: 10.2967/jnumed.117.203877. Epub 2018 Apr 19. PMID: 29674422; PMCID: PMC6910646.
• 19. Haffner MC, Kronberger IE, Ross JS, Sheehan CE, Zitt M, Mühlmann G, et al. Prostate-specific membrane antigen expression in the neovasculature of gastric and colorectal cancers. Human pathology. 2009;40(12):1754-61.
• 20. Morgantetti G, Ng KL, Samaratunga H, Rhee H, Gobe GC, Wood ST. Prostate specific membrane antigen (PSMA) expression in vena cava tumour thrombi of clear cell renal cell carcinoma suggests a role for PSMA-driven tumour neoangiogenesis. Translational andrology and urology. 2019;8(Suppl 2):S147-s55.
• 21. Weidner N. Chapter 14. Measuring intratumoral microvessel density. Methods Enzymol. 2008;444:305-23. doi: 10.1016/ S0076-6879(08)02814-0. PMID: 19007671.
• 22. Heitkötter B, Steinestel K, Trautmann M, Grünewald I, Barth P, Gevensleben H, Bögemann M, Wardelmann E, Hartmann W, Rahbar K, Huss S. Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid. Oncotarget. 2018 Jan 4;9(11):9867-9874. doi: 10.18632/oncotarget.23984. PMID: 29515776; PMCID: PMC5839407.
• 23. 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. Archives of pathology & laboratory medicine. 2011;135(11):1486-9.
• 24. Haffner MC, Laimer J, Chaux A, Schäfer G, Obrist P, Brunner A, et al. High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity. Modern Pathology. 2012;25(8):1079-85.
• 25. Schreiber H, Hänze J, Nimphius W, Verburg FA, Luster M, Hofmann R, et al. Prostate specific membrane antigen (PSMA) in urothelial cell carcinoma (UCC) is associated with tumor grading and staging. Journal of Cancer Research and Clinical Oncology. 2020;146(2):305-13.
• 26. Kasoha M, Unger C, Solomayer E-F, Bohle RM, Zaharia C, Khreich F, et al. Prostate-specific membrane antigen (PSMA) expression in breast cancer and its metastases. Clinical & Experimental Metastasis. 2017;34(8):479-90.
• 27. Klein Nulent TJW, van Es RJJ, Krijger GC, de Bree R, Willems SM, de Keizer B. Prostate-specific membrane antigen PET imaging and immunohistochemistry in adenoid cystic carcinoma- a preliminary analysis. European Journal of Nuclear Medicine and Molecular Imaging. 2017;44(10):1614-21.
• 28. Kim SH, Park WS, Park EY, Park B, Joo J, Joung JY, et al. The prognostic value of BAP1, PBRM1, pS6, PTEN, TGase2, PDL1, CA9, PSMA, and Ki-67 tissue markers in localized renal cell carcinoma: A retrospective study of tissue microarrays using immunohistochemistry. PloS one. 2017;12(6):e0179610.
• 29. Schmidt LH, Heitkötter B, Schulze AB, Schliemann C, Steinestel K, Trautmann M, Marra A, Hillejan L, Mohr M, Evers G, Wardelmann E, Rahbar K, Görlich D, Lenz G, Berdel WE, Hartmann W, Wiewrodt R, Huss S. Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer. PLoS One. 2017 Oct 27;12(10):e0186280. doi: 10.1371/journal. pone.0186280. PMID: 29077706; PMCID: PMC5659610.
• 30. Van de Wiele C, Sathekge M, de Spiegeleer B, De Jonghe PJ, Debruyne PR, Borms M, et al. PSMA expression on neovasculature of solid tumors. Histology and histopathology. 2020;35(9):919-27.