title: Serum RARRES2 Is a Prognostic Marker in Patients With Adrenocortical Carcinoma.
abstract: Retinoic acid receptor responder protein 2 (RARRES2) is a small secreted protein involved in multiple cancers, including adrenocortical carcinoma (ACC). However, discordant tumor and serum RARRES2 levels have been reported in various cancers. The etiology of this discordance is unknown and has not been studied in pair-matched tumor and serum samples.
  
  
  
  To determine tissue and serum RARRES2 levels in patients with adrenocortical neoplasm and to elucidate the prognostic implications of RARRES2 levels.
  
  
  
  Tissue and serum RARRES2 levels were analyzed. A pair-matched analysis was performed to examine tissue and serum RARRES2 from 51 patients with benign adrenocortical tumors and 18 patients with ACC. Overall survival was analyzed based on RARRES2 expression. A mouse xenograft model was used to determine the source of serum RARRES2.
  
  
  
  Patients with ACC had decreased tumor RARRES2 gene expression (P < .0001) and increased serum RARRES2 levels (P < .005) as compared with patients with benign adrenocortical tumors. Higher serum RARRES2 levels were associated with improved overall survival (P = .0227). A mouse xenograft model demonstrated that higher tissue RARRES2 expression was associated with higher RARRES2 secretion in the serum and that there was an intrinsic mechanism in maintaining serum RARRES2 homeostasis.
  
  
  
  Serum and tissue RARRES2 expression levels are paradoxical in patients with ACC. The elevated RARRES2 in patient serum is unlikely to be secreted from tumor cells. Serum RARRES2 may be used as a novel prognostic marker for ACC.
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu-Chittenden
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Dhaval
authors.initials: D
authors.lastname: Patel
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Kelli
authors.initials: K
authors.lastname: Gaskins
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Assie
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Jerome
authors.initials: J
authors.lastname: Bertherat
authors.affiliation: Endocrine Oncology Branch (Y.L.-C., D.P., K.G., E.K.), National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892; Department of Pathology (T.J.G.), University of Michigan, Ann Arbor, Michigan 48109; Institut Cochin (G.A., J.B.), Inserm Unité 1016, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, Descartes University, 75014, Paris, France; and Department of Endocrinology (G.A., J.B.), Reference Center for Rare Adrenal Diseases, Assistance Publique Hôpitaux de Paris, Hôpital Cochin, 75014, Paris, France.
authors.forename: Electron
authors.initials: E
authors.lastname: Kebebew
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D018268:Adrenocortical Carcinoma / Q000097:blood* / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D015153:Blotting, Western; D016022:Case-Control Studies; D018925:Chemokines / Q000097:blood* / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood* / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; C478630:RARRES2 protein, human; D012333:RNA, Messenger