title: Prostate-Specific Membrane Antigen Is a Potential Antiangiogenic Target in Adrenocortical Carcinoma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Expression of PSMA was evaluated in benign and malignant adrenal tumors and 1 patient with metastatic ACC.
  
  
  METHODS
  This study took place at a tertiary referral center.
  
  
  METHODS
  Fifty adrenal samples were evaluated, including 16 normal adrenal glands, 16 adrenocortical adenomas, 15 primary ACC, and 3 ACC metastases.
  
  
  METHODS
  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.
authors.affiliation: 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.
authors.forename: Michael J P
authors.initials: MJ
authors.lastname: Crowley
authors.affiliation: 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.
authors.forename: Theresa
authors.initials: T
authors.lastname: Scognamiglio
authors.affiliation: 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.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: David A
authors.initials: DA
authors.lastname: Kleiman
authors.affiliation: 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.
authors.forename: Toni
authors.initials: T
authors.lastname: Beninato
authors.affiliation: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Aronova
authors.affiliation: 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.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yuliya S
authors.initials: YS
authors.lastname: Jhanwar
authors.affiliation: 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.
authors.forename: Ana
authors.initials: A
authors.lastname: Molina
authors.affiliation: 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.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Tagawa
authors.affiliation: 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.
authors.forename: Neil H
authors.initials: NH
authors.lastname: Bander
authors.affiliation: 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.
authors.forename: Rasa
authors.initials: R
authors.lastname: Zarnegar
authors.affiliation: 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.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: 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.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Fahey
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000098:blood supply* / Q000737:chemistry*; D018246:Adrenocortical Adenoma / Q000098:blood supply / Q000737:chemistry; D000328:Adult; D000368:Aged; D018952:Antigens, CD34 / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis* / Q000235:genetics*; D001808:Blood Vessels / Q000737:chemistry / Q000473:pathology; D005260:Female; D015870:Gene Expression; D043425:Glutamate Carboxypeptidase II / Q000032:analysis* / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000175:diagnosis; D009389:Neovascularization, Pathologic; D049268:Positron-Emission Tomography; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D018952:Antigens, CD34; D000954:Antigens, Surface; D012333:RNA, Messenger; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II