Well-Differentiated Thyroid Cancer Neovasculature Expresses Prostate-Specific Membrane Antigen—a Possible Novel Therapeutic Target Maureen Moore 1 & Suraj Panjwani 1 & Rashmi Mathew 1 & Michael Crowley 1 & Yi-Fang Liu 2 & Anna Aronova 1 & Brendan Finnerty 1 & Rasa Zarnegar 1 & Thomas J. Fahey III 1 & Theresa Scognamiglio 2 Published online: 26 August 2017 # Springer Science+Business Media, LLC 2017 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 pa- tients, 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 expres- sion was not detected in normal thyroid tissue. DTC tumors demonstrated a significantly higher PSMA expression, in re- gard 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 expres- sion was seen more frequently in specimens from distant me- tastases (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. Keywords PSMA . Thyroid cancer . Radioactive iodine . Well-differentiated * Theresa Scognamiglio ths9004@med.cornell.edu Maureen Moore Mud9014@med.cornell.edu Suraj Panjwani Sjp2004@med.cornell.edu Rashmi Mathew rashmimathew4@gmail.com Michael Crowley mic2029@med.cornell.edu Yi-Fang Liu yfliu@med.cornell.edu Anna Aronova ana2019@nyp.org Brendan Finnerty bmf9002@nyp.org Rasa Zarnegar Raz2002@med.cornell.edu Thomas J. Fahey, III tjfahey@med.cornell.edu 1 Department of Surgery, New York Presbyterian Hospital, Weill Cornell Medicine, New York, NY 10065, USA 2 Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, Weill Cornell Medicine, 525 East 68th Street, Starr 10, New York, NY 10065, USA Endocr Pathol (2017) 28:339–344 DOI 10.1007/s12022-017-9500-9