Prostate-specific membrane antigen is a potential antiangiogenic target in adrenocortical carcinoma

Academic Article

Abstract

  • © 2016 by the Endocrine Society. Context: Adrenocortical carcinoma (ACC) is a rare tumor type with a poor prognosis and few therapeutic options. Objective: Assess prostate-specific membrane antigen (PSMA) expression as a potential novel therapeutic target for ACC. Design: Expression of PSMA was evaluated in benign and malignant adrenal tumors and 1 patient with metastatic ACC. Setting: This study took place at a tertiary referral center. Patients: Fifty adrenal samples were evaluated, including 16 normal adrenal glands, 16 adrenocortical adenomas, 15 primary ACC, and 3 ACC metastases. Main Outcome Measures: Demographics, PSMA expression levels via real-time quantitative polymerase chain reactionandimmunohistochemistryandwhole-body positron emission tomographycomputed tomography standardized uptake values for 1 patient. Results: qPCR demonstrated an elevated level ofPSMAinACCrelative to all benign tissues (P=.05). Immunohistochemistry localized PSMA expression to the neovasculature of ACC and confirmed overexpression ofPSMAinACCrelative to benign tissues both in intensityandpercentage of vessels stained (78% of ACC, 0% of normal adrenal, and 3.27% of adenoma-associated neovasculature; P =.001). Those with more than 25% PSMA-positive vessels were 33 times more likely to be malignant than benign (odds ratio, P =.001). Whole-body positron emission tomography-computed tomography imaging showed targeting of anti-PSMA Zr89-J591 to 5/5 of the patient's multiple lung masses with an average measurement of 3.49 ± 1.86 cm and a standardized uptake value of 1.4 ± 0.65 relative to blood pool at 0.8 standardized uptake value. Conclusions: PSMA is significantly overexpressed in ACC neovasculature when compared with normal and benign adrenal tumors. PSMA expression can be used to image ACC metastases in vivo and may be considered as a potential diagnostic and therapeutic target in ACC.
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    Author List

  • Crowley MJP; Scognamiglio T; Liu YF; Kleiman DA; Beninato T; Aronova A; Liu H; Jhanwar YS; Molina A; Tagawa ST
  • Start Page

  • 981
  • End Page

  • 987
  • Volume

  • 101
  • Issue

  • 3