Well-Differentiated Thyroid Cancer Neovasculature Expresses Prostate-Specific Membrane Antigen—a Possible Novel Therapeutic Target

Abstract

Prostate-specific membrane antigen (PSMA), a type II transmembrane glycoprotein receptor, is highly expressed in prostate cancer and in the tumor neovasculature of colon, breast, and adrenocortical tumors. Here, we analyzed PSMA expression in the neovasculature of various thyroid cancer subtypes and assessed whether PSMA expression is correlated with aggressive behavior. From a prospectively maintained database, we evaluated 91 samples from 68 patients, including 37 primary differentiated thyroid cancers (DTCs) [11 classic papillary (cPTC), 9 follicular-variant (FvPTC), 11 follicular (FTC), 6 radioactive iodine-refractory (RAIR)], 5 anaplastic (ATC) carcinomas, 9 distant and 12 lymph node metastases, 21 benign thyroid nodules, and 7 normal thyroid specimens. Formalin-fixed paraffin-embedded tissue blocks were immunostained for vascular endothelial marker CD31 and PSMA with proper controls. PSMA expression was not detected in normal thyroid tissue. DTC tumors demonstrated a significantly higher PSMA expression, in regard to both intensity and percentage of vessels stained, than benign tumors (p < 0.001). Among the histologic subtypes, cPTC, FTC, and RAIR carcinomas demonstrated the highest percent of moderate to strong PSMA staining. PSMA expression was seen more frequently in specimens from distant metastases (100%) compared with specimens from only lymph node metastases (67%). PSMA is significantly overexpressed in the neovasculature of DTCs compared with normal and benign thyroid nodules specifically with increased expression in RAIR carcinomas and distant metastases. PSMA should be further explored as a novel therapeutic target for metastatic and RAIR carcinomas.

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

“…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. No PSMA expression was seen on the tumor cells [13]. Recently, in a study including 59 DTC patients, Sollini et al found PSMA positivity in microvessels in 80%.…”

“…PSMA is also expressed in the neovasculature of other tumors including carcinomas of the lung, breast, colorectum, and thyroid [8][9][10][11][12]. Compared to normal thyroid tissue, PSMA is significantly overexpressed in the neovasculature of DTC, especially in the RAI-refractory type [13]. Altogether, PSMA is a potential target for theranostics in RAI-refractory DTC.…”

Prostate‐specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate

“…In a study examining 91 samples of thyroid cancer, PSMA expression was expressed only in cancer neovasculature and not in the tumour cells, and was not detected in normal thyroid tissue . The subtypes of thyroid cancer where neovasculature expressed the highest levels of PSMA were papillary, radioactive iodine‐refractory and follicular thyroid tumours .…”

PSMA expression level predicts differentiated thyroid cancer aggressiveness and patient outcome

“…The first evidence of PSMA expression in DTC was provided by Verburg et al [11], who performed 68 Ga-PSMA PET/CT imaging of a patient with 131 I-negative scintigraphy who was bearing metastatic poorly differentiated DTC. More recently, immunohistochemical assessment of PSMA expression revealed it to be highly irregularly expressed by thyroid tumors, but not by normal thyroid tissue [12, 14, 15]. PSMA expression has been reported to be significantly associated with tumor size, vascular invasion in follicular carcinoma [12], and poorly or undifferentiated subtypes [14].…”