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J Clin Endocrinol Metab. 2016 Mar;101(3):981-7. doi: 10.1210/jc.2015-4021. Epub 2016 Jan 15.

Prostate-Specific Membrane Antigen Is a Potential Antiangiogenic Target in Adrenocortical Carcinoma.

Author information

1
Departments of Surgery (M.J.P.C., D.A.K., T.B., A.A., R.Z., T.J.F.), Pathology and Laboratory Medicine (T.S., Y.-F.L.), Urology (H.L., S.T.T., N.H.B.), Nuclear Medicine (Y.S.J.), and Medicine (A.M., S.T.T.); New York Presbyterian Hospital-Weill Cornell Medical College and Department of Physiology and Biophysics (M.J.P.C., O.E.), Weill Cornell Medical College-Institute for Computational Biomedicine, New York, New York 10065; and HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine (O.E.), Weill Cornell Medical College, New York, New York 10021.

Abstract

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 reaction and immunohistochemistry and whole-body positron emission tomography-computed tomography standardized uptake values for 1 patient.

RESULTS:

qPCR demonstrated an elevated level of PSMA in ACC relative to all benign tissues (P < .05). Immunohistochemistry localized PSMA expression to the neovasculature of ACC and confirmed overexpression of PSMA in ACC relative to benign tissues both in intensity and percentage 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.

PMID:
26771706
DOI:
10.1210/jc.2015-4021
[Indexed for MEDLINE]
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