Somatostatin Receptor Expression Is Associated With Metastasis and Patient Outcome in Pulmonary Carcinoid Tumors

• Published in: The journal of clinical endocrinology and metabolism Vol. 104; no. 6; pp. 2083 - 2093
• Main Authors: Vesterinen, Tiina, Leijon, Helena, Mustonen, Harri, Remes, Satu, Knuuttila, Aija, Salmenkivi, Kaisa, Vainio, Paula, Arola, Johanna, Haglund, Caj
• Format: Journal Article
• Language: English
• Published: Washington, DC Endocrine Society 01-06-2019; Copyright Oxford University Press; Oxford University Press
• Subjects: Adult; Aged; Aged, 80 and over; Carcinoid Tumor - mortality; Carcinoid Tumor - pathology; Carcinoid Tumor - surgery; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Kaplan-Meier Estimate; Lanreotide; Lung - pathology; Lung - surgery; Lung cancer; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lymph nodes; Male; Medical prognosis; Medical research; Medicine, Experimental; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; Neuroendocrine tumors; Patient outcomes; Patients; Pneumonectomy; Prognosis; Progression-Free Survival; Receptors, Somatostatin - metabolism; Reclassification; Retrospective Studies; Somatostatin; Somatostatin receptors; Surgery; Time Factors; Tissue Array Analysis; Tumors; Young Adult; Finland
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2018-01931

Abstract
Context
Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs.
Objective
To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data.
Design, Setting, and Patients
This retrospective study was conducted at Helsinki University Hospital and University of Helsinki. It included 178 PC tumors coupled with patients’ clinical data retrieved through Finnish biobanks. After histological reclassification, tissue specimens were processed into next-generation tissue microarray format and stained immunohistochemically with monoclonal SSTR1 to SSTR5 antibodies.
Main Outcome Measure
SSTR1 to SSTR5 expression in PC tumors.
Results
Expression of SSTR1 to SSTR5 was detected in 52%, 75%, 56%, 16%, and 32% of the tumors, respectively. Membrane-bound staining was observed for all receptors. SSTR2 negativity and SSTR4 positivity was associated with lymph node involvement at the time of surgery (P = 0.014 and P = 0.017, respectively) and with distant metastasis (P = 0.027 and P = 0.015, respectively). SSTR3 and SSTR4 expression was associated with increased risk of shorter survival [P = 0.046, hazard ratio (HR) 4.703, 95% CI 1.027 to 21.533; and P = 0.013, HR 6.64, 95% CI 1.48 to 29.64, respectively], whereas expression of SSTR1 and SSTR2 was associated with improved outcome (P = 0.021, HR 0.167, 95% CI 0.037 to 0.765; and P = 0.022, HR 0.08, 95% CI 0.01 to 0.70, respectively).
Conclusion
SSTR1 to SSTR5 expression is observed in PCs. As SSTR expression is associated with the tumor’s metastatic potential and patient outcome, these receptors may offer the possibility for individualized prognosis estimation.
Pulmonary carcinoid tumors express all five somatostatin receptors (SSTRs). Immunohistochemical expression of SSTR3 or SSTR4 or lack of expression of SSTR1 or SSTR2 are potential prognostic factors.