Neovascular PSMA expression is a common feature in malignant neoplasms of the thyroid.

Birthe Heitkötter,Heidrun Gevensleben,Martin Bögemann,Wolfgang Hartmann,Kambiz Rahbar,Sebastian Huss,Eva Wardelmann,Konrad Steinestel,Peter Barth,Inga Grünewald,Marcel Trautmann

doi:10.18632/oncotarget.23984

Abstract

AimPSMA (prostate-specific membrane antigen) is physiologically expressed in normal prostate tissue and over expressed in prostate cancer cells, therefore constituting a potential target for antibody-based radioligand therapy. Very recent imaging findings reported PSMA-PET/CT uptake in various thyroid lesions. We were therefore encouraged to systematically analyse PSMA expression in different benign and malignant thyroid lesions.MethodsImmunohistochemistry was used to detect PSMA expression in 101 thyroid lesions, while neovasculature was identified by CD34 immunostaining.ResultsPSMA expression in the neovasculature was significantly more frequent in malignant tumors (36/63; 57.1%) compared to benign diseases (5/38; 13.2%; p = 0.0001). In addition, PSMA expression levels in the neovasculature of poorly and undifferentiated thyroid cancers were significantly higher compared to differentiated thyroid tumors (p = 0.021). However, one case with a strong expression in follicular adenoma was identified.ConclusionsWe conclude that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma. High expression in the tumor-associated neovasculature is predominantly found in poorly differentiated and undifferentiated (anaplastic) thyroid cancer. This knowledge is highly relevant when interpreting PSMA/PET-CT scans from patients with prostate cancer. In addition, our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer.

Highlights

prostate specific membrane antigen (PSMA) is a 100 kDa type II-transmembrane glycoprotein with both intra- and extracellular protein domains exerting folate hydrolase and neurocarboxypeptidase activity [1, 2]
We conclude that neovascular PSMA expression is common in thyroid cancer but may rarely be found in benign thyroid diseases, such as follicular adenoma
Our findings might provide a rationale for further evaluation of PSMA-targeted anti-neovascular or radioligand therapy in metastatic dedifferentiated thyroid cancer

Summary

Introduction

PSMA (prostate specific membrane antigen) is a 100 kDa type II-transmembrane glycoprotein with both intra- and extracellular protein domains exerting folate hydrolase and neurocarboxypeptidase activity [1, 2]. PSMA-based radioligand therapy has been established as a therapeutic regimen in metastatic prostate cancer [2, 5,6,7,8,9,10,11]. Functional studies revealed that the role of PSMA in tumor angiogenesis is part of an autoregulatory loop involving β1-integrin and p21-activated kinase 1 (PAK1). In this context, active PSMA facilitates endothelial cell invasion through the extracellular matrix by interacting with the cytoskeleton via integrin signaling and actinbinding protein Filamin A [7, 17]

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