Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors

Zhi Rong Qian, Tingting Li, Monica Ter-Minassian, Juhong Yang, Jennifer A. Chan, Lauren K. Brais, Yohei Masugi, Arunthathi Thiaglingam, Nichole Brooks, Reiko Nishihara, Mireille Bonnemarie, Atsuhiro Masuda, Kentaro Inamura, Sun A. Kim, Kosuke Mima, Yasutaka Sukawa, Ruoxu Dou, Xihong Lin, David C. Christiani, Fabien SchmidlinCharles S. Fuchs, Umar Mahmood, Shuji Ogino, Matthew H. Kulke

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 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.

Original languageEnglish
JournalPancreas
DOIs
Publication statusAccepted/In press - 2016 Sep 12

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Somatostatin Receptors
Neuroendocrine Tumors
Somatostatin
Survival
Disease-Free Survival
Proxy
Small Intestine
Immunohistochemistry
Regression Analysis
Confidence Intervals
Neoplasm Metastasis
Genes
Neoplasms

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Endocrinology

Cite this

Qian, Z. R., Li, T., Ter-Minassian, M., Yang, J., Chan, J. A., Brais, L. K., ... Kulke, M. H. (Accepted/In press). Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors. Pancreas. https://doi.org/10.1097/MPA.0000000000000700

Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors. / Qian, Zhi Rong; Li, Tingting; Ter-Minassian, Monica; Yang, Juhong; Chan, Jennifer A.; Brais, Lauren K.; Masugi, Yohei; Thiaglingam, Arunthathi; Brooks, Nichole; Nishihara, Reiko; Bonnemarie, Mireille; Masuda, Atsuhiro; Inamura, Kentaro; Kim, Sun A.; Mima, Kosuke; Sukawa, Yasutaka; Dou, Ruoxu; Lin, Xihong; Christiani, David C.; Schmidlin, Fabien; Fuchs, Charles S.; Mahmood, Umar; Ogino, Shuji; Kulke, Matthew H.

In: Pancreas, 12.09.2016.

Research output: Contribution to journalArticle

Qian, ZR, Li, T, Ter-Minassian, M, Yang, J, Chan, JA, Brais, LK, Masugi, Y, Thiaglingam, A, Brooks, N, Nishihara, R, Bonnemarie, M, Masuda, A, Inamura, K, Kim, SA, Mima, K, Sukawa, Y, Dou, R, Lin, X, Christiani, DC, Schmidlin, F, Fuchs, CS, Mahmood, U, Ogino, S & Kulke, MH 2016, 'Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors', Pancreas. https://doi.org/10.1097/MPA.0000000000000700
Qian, Zhi Rong ; Li, Tingting ; Ter-Minassian, Monica ; Yang, Juhong ; Chan, Jennifer A. ; Brais, Lauren K. ; Masugi, Yohei ; Thiaglingam, Arunthathi ; Brooks, Nichole ; Nishihara, Reiko ; Bonnemarie, Mireille ; Masuda, Atsuhiro ; Inamura, Kentaro ; Kim, Sun A. ; Mima, Kosuke ; Sukawa, Yasutaka ; Dou, Ruoxu ; Lin, Xihong ; Christiani, David C. ; Schmidlin, Fabien ; Fuchs, Charles S. ; Mahmood, Umar ; Ogino, Shuji ; Kulke, Matthew H. / Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors. In: Pancreas. 2016.
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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 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.",
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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.

PY - 2016/9/12

Y1 - 2016/9/12

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.

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