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.

中文翻译：

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甲状腺肿瘤微血管中的PSMA表达-对PSMA治疗学的潜在影响。

前列腺特异性膜抗原（PSMA）在前列腺癌上皮细胞中过表达，使其成为分子成像和治疗的有希望的靶标。最近，一些研究发现甲状腺肿瘤，包括放射性碘难治性（RAIR）癌症，意外摄取了PSMA放射性示踪剂。在各种恶性肿瘤的肿瘤相关内皮中都报道了PSMA表达，但是在甲状腺肿瘤中尚未系统地解决这一问题。我们发现PSMA通常在甲状腺肿瘤的微血管中表达（120/267），但在甲状腺的良性组织中却不表达。新血管中的PSMA表达高度不规则，良性肿瘤中的PSMA表达为19％，甲状腺癌中的PSMA表达超过50％。这种异质性不直接归因于内皮细胞的增殖，正如用增殖相关的内皮标记CD105免疫染色所证实的那样。PSMA表达与滤泡癌的肿瘤大小（p = 0.02）和血管浸润（p = 0.03）相关，而与其他基线组织学和临床参数无关。重大的翻译含义是RAIR肿瘤和高级别癌症可维持高水平的PSMA表达，并且可以被PSMA配体放射性药物靶向。我们的研究预测了与甲状腺PSMA成像潜在相关的几个陷阱，例如在慢性甲状腺炎的树突状细胞中，在包涵体肿瘤中的低表达，缺乏器官特异性和PSMA阳性，这是首次被描述。重大的翻译含义是RAIR肿瘤和高级别癌症可维持高水平的PSMA表达，并且可以被PSMA配体放射性药物靶向。我们的研究预测了与甲状腺PSMA成像潜在相关的几个陷阱，例如在慢性甲状腺炎的树突状细胞中，在包涵体肿瘤中的低表达，缺乏器官特异性和PSMA阳性，这是首次被描述。重大的翻译含义是RAIR肿瘤和高级别癌症可维持高水平的PSMA表达，并且可以被PSMA配体放射性药物靶向。我们的研究预测了与甲状腺PSMA成像潜在相关的几个陷阱，例如在慢性甲状腺炎的树突状细胞中，在吞噬性肿瘤中的低表达，缺乏器官特异性和PSMA阳性，这是首次被描述。