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      Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

      research-article
      , MD, PhD, , MD, PhD, , ScD, , MD, PhD, , MD, MPH, , MPH, , MD, PhD, , PhD, , BS, , PhD, , MD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, PhD, , MD, , PhD, , MD, MPH, , PhD, , MD, MPH, , MD, , MD, PhD, MS, , MD, MMsc
      Pancreas
      somatostatin receptor, somatostatin analog, prognosis, progression-free survival and overall survival, carcinoid, neuroendocrine tumor

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          Abstract

          Objective

          Somatostatin receptors (SSTRs), products of gene superfamily SSTR1- 5, are commonly expressed in neuroendocrine tumors (NETs). Somatostatin analogs (SSAs) bind to SSTRs and are used as therapeutic agents in patients with advanced NETs. We hypothesized that tumor SSTR expression status would be associated with clinical outcomes in NET.

          Methods

          Expression of the five SSTRs was evaluated by immunohistochemistry, using tissue microarrays comprising 173 primary NETs, 24 matched metastases, and 22 metastatic NETs from 195 patients. Cox proportional hazards regression analysis was used to assess the association of SSTR expression status (high vs. low) with clinical outcomes, adjusting for potential confounders.

          Results

          High expression of SSTR2 was associated with longer overall survival in the cohort overall (multivariate hazard ratio 0.42, 95% confidence interval 0.21–0.84; P = 0.013). In a subgroup of patients with metastatic small intestine NET treated with SSAs and evaluable for progression, SSTR2 expression was associated with both longer progression-free and overall survival. No associations with progression-free or overall survival were observed with expression of other SSTRs.

          Conclusions

          Our study demonstrated that expression of SSTR2, but not other SSTRs, is associated with longer overall survival. In patients treated with SSAs, expression of SSTR2 is associated with longer progression-free survival.

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          Author and article information

          Contributors
          Journal
          8608542
          6627
          Pancreas
          Pancreas
          Pancreas
          0885-3177
          1536-4828
          6 July 2016
          November 2016
          01 November 2017
          : 45
          : 10
          : 1386-1393
          Affiliations
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA; Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          IPSEN Bioscience Inc., Global Drug Discovery department, Cambridge, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          IPSEN Innovation, Global Drug Discovery department, Les Ulis, France
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
          Department of Environmental Health and Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. Massachusetts General Hospital, Harvard Medical School, Boston, MA
          IPSEN Innovation, Global Drug Discovery department, Les Ulis, France
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA
          Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA. Department of Pathology, Brigham and Women’s Hospital, and Harvard Medical School, Boston, MA
          Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA
          Author notes
          Corresponding author: Zhi Rong Qian, MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, 450 Brookline Ave., Room MA420, Boston, MA 02115 USA, Telephone: 617-582-9145; Fax: 617-582-855; Zhirong_Qian@ 123456dfci.harvard.edu

          Zhi Rong Qian and Tingting Li contributed equally.

          Article
          PMC5067972 PMC5067972 5067972 nihpa796227
          10.1097/MPA.0000000000000700
          5067972
          27622342
          0d6ddaef-dcf4-44d2-9caa-34f63a464685
          History
          Categories
          Article

          neuroendocrine tumor,somatostatin receptor,somatostatin analog,prognosis,progression-free survival and overall survival,carcinoid

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