TY - JOUR
T1 - Association between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors
AU - Qian, Zhi Rong
AU - Li, Tingting
AU - Ter-Minassian, Monica
AU - Yang, Juhong
AU - Chan, Jennifer A.
AU - Brais, Lauren K.
AU - Masugi, Yohei
AU - Thiaglingam, Arunthathi
AU - Brooks, Nichole
AU - Nishihara, Reiko
AU - Bonnemarie, Mireille
AU - Masuda, Atsuhiro
AU - Inamura, Kentaro
AU - Kim, Sun A.
AU - Mima, Kosuke
AU - Sukawa, Yasutaka
AU - Dou, Ruoxu
AU - Lin, Xihong
AU - Christiani, David C.
AU - Schmidlin, Fabien
AU - Fuchs, Charles S.
AU - Mahmood, Umar
AU - Ogino, Shuji
AU - Kulke, Matthew H.
N1 - Funding Information:
This study was funded in part from a grant from Ipsen Pharmaceuticals. This work was also supported by US National Institutes of Health grants P50 CA127003 to C.S.F., R01 CA151532 to M.H.K., R01 CA151993 to S.O., R35 CA197735 to S.O., R01 CA166582 to U.M., and K07 CA190673 to R.N.
Publisher Copyright:
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/11/1
Y1 - 2016/11/1
N2 - 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.
AB - 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.
KW - neuroendocrine tumor
KW - prognosis
KW - somatostatin analog
KW - somatostatin receptor
KW - survival
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U2 - 10.1097/MPA.0000000000000700
DO - 10.1097/MPA.0000000000000700
M3 - Article
C2 - 27622342
AN - SCOPUS:84987605286
SN - 0885-3177
VL - 45
SP - 1386
EP - 1393
JO - Pancreas
JF - Pancreas
IS - 10
ER -
