Somatostatin Receptor SSTR-2a Expression Is a Stronger Predictor for Survival Than Ki-67 in Pancreatic Neuroendocrine Tumors

Abstract

Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival.This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs.This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed.A total of 99 cases were included in this study. The mean age was 57.8 years (18–87 years) and median tumor size was 25 mm (range 8–160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1–0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1–5.7).Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs.

Peptide receptor radionuclide therapy in patients with medullary thyroid carcinoma: predictors and pitfalls

“…In the present study SSTR2a expression was absent in all 6 patients with PD, which suggests that lack of SSTR2a expression in the tissue biopsy may be a bad prognostic sign in patients with MTC. This is in line with pancreatic NET (P-NETs) and GEP-NETs, where low SSTR2a tumor expression has been shown to be associated with poor outcome and more aggressive grades of tumor [28][29][30]. In a retrospective study in 97 patients with MTC, SSTR2a expression was significantly correlated with the presence of lymph node metastasis.…”

P53, Somatostatin receptor 2a and Chromogranin A immunostaining as prognostic markers in high grade gastroenteropancreatic neuroendocrine neoplasms

“…In a large prospective trial of 279 NET patients, SSTR-2a IHC proved to be an independent prognostic marker for overall survival and confirmed that SSTR-2a IHC correlated with SSTR2-imaging [30]. Another study including 99 pancreatic NET also found expression of SSTR-2a to be an independent positive prognostic factor for survival even superior to Ki67 [31].…”

International Union of Basic and Clinical Pharmacology. CV. Somatostatin Receptors: Structure, Function, Ligands, and New Nomenclature

“…SST 2 expression was also found to be higher in functioning than in nonfunctioning tumors ( Zamora et al, 2010 ; Song et al, 2016 ) and more pronounced in gastroenteric than in pancreatic neoplasms ( Zamora et al, 2010 ). Negative correlation between SST 2 expression and tumor grading or proliferation rate and a positive association with patient outcomes have been shown ( Corleto et al, 2009 ; Srirajaskanthan et al, 2009 ; Zamora et al, 2010 ; Okuwaki et al, 2013 ; Kaemmerer et al, 2015b ; Mehta et al, 2015 ; Qian et al, 2016 ; Song et al, 2016 ; Wang et al, 2017 ). Furthermore, a positive correlation between SST 2 expression and SST-based imaging was demonstrated ( Srirajaskanthan et al, 2009 ; Diakatou et al, 2015 ; Kaemmerer et al, 2015b ).…”

“…Very low levels of SST 2 were also observed in lymphomas ( Dalm et al, 2004 ; Stollberg et al, 2016 ; Ruuska et al, 2018 ). SST 2 represents by far the most prominent SST subtype detected in gastroenteropancreatic (GEP)-NETs, and, overall, it was identified in >70% of cases at a high expression intensity ( Kulaksiz et al, 2002 ; Fischer et al, 2008 ; Corleto et al, 2009 ; Srirajaskanthan et al, 2009 ; Zamora et al, 2010 ; Lupp et al, 2011 ; Okuwaki et al, 2013 ; Kaemmerer et al, 2015b ; Mehta et al, 2015 ; Qian et al, 2016 ; Wang et al, 2017 ). However, SST 2 was detected more frequently in gastrinomas (100%) and in carcinoid tumors (86%) ( Fig.…”