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Abstract
Prostate-specific membrane antigen (PSMA) is overexpressed in prostate cancer epithelium, making it a promising target for molecular imaging and therapy. Recently, several studies found unexpected PSMA radiotracer uptake by thyroid tumors, including radioiodine-refractory (RAIR) cancers. PSMA expression was reported in tumor-associated endothelium of various malignancies, however it has not been systematically addressed in thyroid tumors. We found that PSMA was frequently expressed in microvessels of thyroid tumors (120/267), but not in benign thyroid tissue. PSMA expression in neovasculature was highly irregular ranging from 19% in benign tumors to over 50% in thyroid cancer. Such heterogeneity was not directly attributed to endothelial cell proliferation as confirmed by immunostaining with proliferation-associated endothelial marker CD105. PSMA expression was associated with tumor size (p = 0.02) and vascular invasion in follicular carcinoma (p = 0.03), but not with other baseline histological, and clinical parameters. Significant translational implication is that RAIR tumors and high-grade cancers maintain high level of PSMA expression, and can be targeted by PSMA ligand radiopharmaceuticals. Our study predicts several pitfalls potentially associated with PSMA imaging of the thyroid, such as low expression in oncocytic tumors, absence of organ specificity, and PSMA-positivity in dendritic cells of chronic thyroiditis, which is described for the first time.
Highlights
Prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein highly restricted to prostate epithelium[1, 2]
Prostate-specific membrane antigen (PSMA) in tumor capillaries was expressed in 19% follicular adenomas (FA), 46% follicular carcinomas (FTC), 51% papillary carcinomas (PTC), and 40–50% high-grade thyroid cancers
Our results indicate that PSMA immunoreactivity is frequent in thyroid tumors, being attributed to endothelial, but not epithelial expression
Summary
Prostate specific membrane antigen (PSMA) is a type II transmembrane glycoprotein highly restricted to prostate epithelium[1, 2]. It has promising therapeutic potential, being a carrier for radionuclides directed against cancer cells. Wide use of 68Ga-PSMA PET/CT for prostate imaging yielded a plethora of reports with unexpected detection of non-prostate tumors, including primary and metastatic breast, renal, neuroendocrine and other malignancies[17, 22]. Several consecutive case reports described 68Ga-PSMA-positive thyroid tumors, including adenoma[23,24,25] and carcinoma[26,27,28] Many of these tumors were detected incidentally in patients screened for prostate cancer. A study of a large cohort of thyroid tumors would be desirable to further elucidate these issues and potentially advocate the use of PSMA-based imaging in thyroid patients[32]
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