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Published on: April 17, 2019
Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors
Zhi Rong Qian1, Tingting Li, Monica Ter-Minassian
1From the *Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; †Department of Geriatric Gastroenterology, Chinese PLA General Hospital, Beijing, China; ‡Department of Environmental Health, Harvard T.H. Chan School of Public Health, 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; ∥IPSEN Bioscience Inc, Global Drug Discovery Department, Cambridge, MA; ¶IPSEN Innovation, Global Drug Discovery Department, Les Ulis, France; Departments of #Biostatistics, and **Epidemiology, Harvard T.H. Chan School of Public Health, ††Massachusetts General Hospital, ‡‡Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, §§Department of Radiology, Massachusetts General Hospital, and ∥∥Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
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 5 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 (OS) 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 survival (PFS) and OS. No associations with PFS or OS were observed with expression of other SSTRs.
Conclusions:
Our study demonstrated that expression of SSTR2, but not other SSTRs, is associated with longer OS. In patients treated with SSAs, expression of SSTR2 is associated with longer PFS survival.
