본문 바로가기
KERD
논문KCI 등재

Clinical Significance of Protein Expression of Cyclooxygenase-2 and Somatostatin Receptors in Gastroenteropancreatic Neuroendocrine Tumors

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

주제분류의학일반

초록

Purpose This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Materials and Methods Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. Results COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). Conclusion Our results suggest that expression of SSTR subtypes is associated with favorable prognosis,whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together,COX2 could be a possible therapeutic target in some subsets of GEP-NETs.

Abstract

Purpose This study was undertaken to evaluate the significance of cyclooxygenase-2 (COX2) overexpression and the expression of somatostatin receptor (SSTR) subtypes in gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Materials and Methods Two hundred and forty-seven cases of GEP-NET, comprising 86 foregut and 156 hindgut primary NETs, and 5 metastatic NETs in the liver, were studied retrospectively with immunohistochemistry for COX2, chromogranin A, Ki-67, SSTR1, SSTR2, and SSTR5. Results COX2 overexpression was observed in 54%(126 of 234), and SSTR1, SSTR2, and SSTR5 positivity in 84%(196 of 233), 72%(168 of 233), and 55%(128 of 232), respectively. COX2 overexpression was found to be positively correlated with Ki-67 labeling index and inversely correlated with the expression of SSTR subtypes. In addition, the expression of SSTR subtypes was tightly correlated in any comparative pairs. A significant inverse correlation was found between COX2and SSTR2 expression in the foregut, but not hindgut NETs. Kaplan-Meier analyses showed that COX2 overexpression (p=0.003) and high Ki-67 labeling index (p<0.001) were associated with poor overall survival (OS), whereas expression of SSTR2 (p<0.001) was associated with better OS of GEP-NET patients. Multivariate analysis revealed negative SSTR2 expression as an independent prognostic marker in GEP-NET patients (p<0.001). Conclusion Our results suggest that expression of SSTR subtypes is associated with favorable prognosis,whereas COX2 overexpression is associated with poor prognosis in GEP-NETs. Taken together,COX2 could be a possible therapeutic target in some subsets of GEP-NETs.

참고문헌 (24)

  1. Oberg K, "Endocrine tumours of the pancreas", Best Pract Res Clin Gastroenterol, 19, pp.753~781 (2005)
  2. Plöckinger U, "Guidelines for the diagnosis and treatment of neuroendocrine gastrointestinal tumours: a consensus statement on behalf of the European Neuroendocrine Tumour Society (ENETS)", Neuroendocrinology, 80, pp.394~424 (2004)
  3. Nakajima T, "Why is cyclooxygenase-2 expressed in neuroendocrine cells of the human alimentary tract", Pathol Int, 47, pp.889~891 (1997)
  4. Detjen KM, "Nonsteroidal anti-inflammatory drugs inhibit growth of human neuroendocrine tumor cells via G1 cell-cycle arrest", Int J Cancer, 107, pp.844~853 (2003)
  5. Cadden I, "An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours", Neuroendocrinology, 86, pp.104~111 (2007)
  6. Ohike N, "Immunohistochemical analysis of cyclooxygenase (COX)-2 expression in pancreatic endocrine tumors: association with tumor progression and proliferation", Pathol Int, 51, pp.770~777 (2001)
  7. Volante M, "Somatostatin receptors and their interest in diagnostic pathology", Endocr Pathol, 15, pp.275~291 (2004)
  8. Eriksson B, "Summing up 15 years of somatostatin analog therapy in neuroendocrine tumors: future outlook", Ann Oncol, 10(2), pp.S31~S38 (1999)
  9. Missiaglia E, "Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway", J Clin Oncol, 28, pp.245~255 (2010)
  10. Butturini G, "Predictive factors of efficacy of the somatostatin analogue octreotide as first line therapy for advanced pancreatic endocrine carcinoma", Endocr Relat Cancer, 13, pp.1213~1221 (2006)
  11. Greene FL, "AJCC cancer staging manual" (2002), Springer-Verlag
  12. Solcia E, "International histological classification of tumours", pp.38~74 (2000), Springer-Verlag
  13. Kostopoulos I, "Evaluation of the prognostic value of HER-2 and VEGF in breast cancer patients participating in a randomized study with dose-dense sequential adjuvant chemotherapy", Breast Cancer Res Treat, 96, pp.251~261 (2006)
  14. Ito T, "Epidemiological study of gastroenteropancreatic neuroendocrine tumors in Japan", J Gastroenterol, 45, pp.234~243 (2010)
  15. Okami J, "An immunohistochemical study of cyclooxygenase (COX)-2 expression in endocrine tumors of the pancreas", J Exp Clin Cancer Res, 21, pp.569~576 (2002)
  16. Keun-SangKwon, "Sodium Salicylate Inhibits Expression of COX-2 Through Suppression of ERK and Subsequent NF-κB Activation in Rat Ventricular Cardiomyocytes", Archives of Pharmacal Research, 26(7), pp.545~553 (2003), 대한약학회
  17. Tang C, "Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer", Int J Cancer, 112, pp.470~474 (2004)
  18. Huang MT, "Preoperative growth inhibition of human gastric adenocarcinoma treated with a combination of celecoxib and octreotide", Acta Pharmacol Sin, 28, pp.1842~1850 (2007)
  19. Rinke A, "Placebocontrolled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group", J Clin Oncol, 27, pp.4656~4663 (2009)
  20. Schally AV, "Chemotherapy targeted to cancers through tumoral hormone receptors", Trends Endocrinol Metab, 15, pp.300~310 (2004)
  21. Buscail L, "Loss of sst2 somatostatin receptor gene expression in human pancreatic and colorectal cancer", Cancer Res, 56, pp.1823~1827 (1996)
  22. Slaby O, "Gene expression of somatostatin receptor 4 predicts clinical outcome of patients with metastatic neuroendocrine tumors treated with somatostatin analogs", Cancer Biother Radiopharm, 25, pp.237~243 (2010)
  23. Taboada GF, "Impact of gsp oncogene on the mRNA content for somatostatin and dopamine receptors in human somatotropinomas", Neuroendocrinology, 93, pp.40~47 (2011)
  24. Papotti M, "Expression of somatostatin receptor types 1-5 in 81 cases of gastrointestinal and pancreatic endocrine tumors. A correlative immunohistochemical and reverse-transcriptase polymerase chain reaction analysis", Virchows Arch, 440, pp.461~475 (2002)

관련 논문AI추천

SSTR2A Protein Expression in Neuroendocrine Neoplasms of the Colorectum김경미, 김영은, 박영석, 이지연대한병리학회 · Journal of Pathology and Translational Medicine2011 · 제45권 제3호p27 Loss Is Associated with Poor Prognosis in Gastroenteropancreatic Neuroendocrine Tumors김우호, 김희성, 남경한, 이혜승, 최지운대한암학회 · Cancer Research and Treatment2014 · 제46권 제4호Clinical and Prognostic Significances of Cytokeratin 19 and KIT Expression in Surgically Resectable Pancreatic Neuroendocrine Tumors김송철, 김주영, 손은미, 송기병, 안소연, 유은실, 홍승모대한병리학회 · Journal of Pathology and Translational Medicine2015 · 제49권 제1호Proposal for a Standardized Pathology Report of Gastroenteropancreatic Neuroendocrine Tumors: Prognostic Significance of Pathological Parameters강대영, 강윤경, 김경미, 김미정, 김우호, 김윤화, 김준미, 김현기, 손진희, 정은선, 조미연, 진소영, 최은희, 최준혁대한병리학회 · Journal of Pathology and Translational Medicine2013 · 제47권 제3호Expression of Cyclooxygenase-2 and Tumor Microvessel Density in Colorectal Cancer손진희, 이봉화, 채승완, Eo Jin Kim, Eun Yoon Cho대한암학회 · Cancer Research and Treatment2003 · 제35권 제5호Current Trends of the Incidence and Pathological Diagnosis of Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) in Korea 2000-2009: Multicenter Study주미, 강대영, 강미선, 강윤경, 구미진, 국명철, 김경미, 김미정, 김수진, 김우호, 김윤화, 김준미, 김현기, 김희경, 문우성, 박도윤, 박문일, 배한익, 손진희, 윤선오, 이재혁, 장세진, 장희경, 정은선, 조미연, 조창호, 진소영, 최준혁대한암학회 · Cancer Research and Treatment2012 · 제44권 제3호

이 간행물의 다른 논문 (9건)