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

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.

68Ga-PSMA PET/CT in radioactive iodine-refractory differentiated thyroid cancer and first treatment results with 177Lu-PSMA-617

“…Lodewijk et al found PSMA positivity in neovasculature in more than 92% of medullary thyroid carcinoma, while the tumor cells were PSMA negative [22]. Heitkötter et al studied PSMA on IHC in PTC and follicular thyroid carcinoma and found positivity in tumor-associated neovasculature in 18 out of 31 and 4 out of 10 patients, respectively [23]. Moore et al investigated 37 patients and found PSMA significantly overexpressed in the neovasculature of DTC, particularly in RAI-refractory patients and in distant metastases.…”

Potential Applications of 68Ga-PSMA-11 PET/CT in the Evaluation of Salivary Gland Uptake Function: Preliminary Observations and Comparison with 99mTcO4− Salivary Gland Scintigraphy

“…A study by Silver et al showed no expression of PSMA in the thyroid gland [24]. A previous study has shown that neovascular PSMA expression is common in thyroid cancer but may also rarely be found in benign thyroid diseases, such as follicular adenoma [25]. (d) 68 Ga-PSMA-11 PET/CT can provide accurate localization and quantitative analysis for lacrimal glands.…”

Multimodality Imaging of Prostate Cancer

“…Although the name implies specificity, PSMA expression is by no means exclusive to the prostate. There is physiologic high expression in the kidneys and small intestines and abnormal expression in a variety of benign and malignant nonprostatic processes, such as benign skeletal abnormalities (fractures, fibrous dysplasia) and other cancers (23,24). PSMA uptake in nonprostatic malignancies is related to PSMA expression of the tumor-related neovasculature (25).…”