Skip to main content
Top
Published in: Tumor Biology 4/2015

01-04-2015 | Research Article

Tumor-infiltrating neutrophils predict poor outcome in adenocarcinoma of the esophagogastric junction

Authors: Pingping Hu, Zhaofei Pang, Hongchang Shen, Guanghui Wang, Haifeng Sun, Jiajun Du

Published in: Tumor Biology | Issue 4/2015

Login to get access

Abstract

Tumor-infiltrating neutrophil (TIN) has been reported to be an independent predictor in multiple tumors, but its role in the development of adenocarcinoma of the esophagogastric junction (AEG) remains unclear. We conducted immunohistochemistry (IHC) to detect the expression of TIN in 113 consecutive patients with primary AEG. The prognostic value and its relationship with clinicopathological characteristics and Ki-67 (a proliferation-associated antigen) expression were analyzed. High level of TIN was related to poor outcome in AEG patients with a hazard ratio (HR) of 3.93 (95 % confidence interval (CI) = 2.14–7.19, p < 0.001) in univariate analysis and a HR of 3.44 (95 % CI = 1.85–6.37, p < 0.001) in multivariate analysis. In addition, TIN was positively correlated with Ki-67 expression (p = 0.008). Our study found that TIN expression was an independent unfavorable predictor in AEG. Furthermore, the relationship between TIN and Ki-67 indicated that TIN was associated with tumor proliferation, which might provide a potential mechanism for why TIN was related to poor outcome in AEG.
Literature
1.
go back to reference El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol. 2007;5:17–26.CrossRefPubMed El-Serag HB. Time trends of gastroesophageal reflux disease: a systematic review. Clin Gastroenterol Hepatol. 2007;5:17–26.CrossRefPubMed
2.
go back to reference Bredenoord AJ, Pandolfino JE, Smout AJ. Gastro-oesophageal reflux disease. Lancet. 2013;381:1933–42.CrossRefPubMed Bredenoord AJ, Pandolfino JE, Smout AJ. Gastro-oesophageal reflux disease. Lancet. 2013;381:1933–42.CrossRefPubMed
3.
go back to reference Henteleff HJ, Darling G, CAGS Evidence Based Reviews in Surgery Group. Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 6. “GERD” as a risk factor for esophageal cancer. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. Can J Surg J. 2003;46:208–10. Henteleff HJ, Darling G, CAGS Evidence Based Reviews in Surgery Group. Canadian Association of General Surgeons Evidence Based Reviews in Surgery. 6. “GERD” as a risk factor for esophageal cancer. Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma. Can J Surg J. 2003;46:208–10.
4.
go back to reference Carr JS, Zafar SF, Saba N, Khuri FR, El-Rayes BF. Risk factors for rising incidence of esophageal and gastric cardia adenocarcinoma. J Gastrointest Cancer. 2013;44:143–51.CrossRefPubMed Carr JS, Zafar SF, Saba N, Khuri FR, El-Rayes BF. Risk factors for rising incidence of esophageal and gastric cardia adenocarcinoma. J Gastrointest Cancer. 2013;44:143–51.CrossRefPubMed
5.
6.
go back to reference Riesco A. Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils. Cancer. 1970;25:135–40.CrossRefPubMed Riesco A. Five-year cancer cure: relation to total amount of peripheral lymphocytes and neutrophils. Cancer. 1970;25:135–40.CrossRefPubMed
7.
go back to reference Donskov F, von der Maase H. Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol. 2006;24:1997–2005.CrossRefPubMed Donskov F, von der Maase H. Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol. 2006;24:1997–2005.CrossRefPubMed
8.
go back to reference Jensen TO, Schmidt H, Moller HJ, Donskov F, Hoyer M, Sjoegren P, et al. Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma. Cancer. 2012;118:2476–85.CrossRefPubMed Jensen TO, Schmidt H, Moller HJ, Donskov F, Hoyer M, Sjoegren P, et al. Intratumoral neutrophils and plasmacytoid dendritic cells indicate poor prognosis and are associated with pSTAT3 expression in AJCC stage I/II melanoma. Cancer. 2012;118:2476–85.CrossRefPubMed
9.
go back to reference Rao HL, Chen JW, Li M, Xiao YB, Fu J, Zeng YX, et al. Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients’ adverse prognosis. PLoS One. 2012;7:e30806.CrossRefPubMedPubMedCentral Rao HL, Chen JW, Li M, Xiao YB, Fu J, Zeng YX, et al. Increased intratumoral neutrophil in colorectal carcinomas correlates closely with malignant phenotype and predicts patients’ adverse prognosis. PLoS One. 2012;7:e30806.CrossRefPubMedPubMedCentral
10.
go back to reference Warth A, Cortis J, Soltermann A, Meister M, Budczies J, Stenzinger A, et al. Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer. 2014;111:1222–9.CrossRefPubMedPubMedCentral Warth A, Cortis J, Soltermann A, Meister M, Budczies J, Stenzinger A, et al. Tumour cell proliferation (Ki-67) in non-small cell lung cancer: a critical reappraisal of its prognostic role. Br J Cancer. 2014;111:1222–9.CrossRefPubMedPubMedCentral
11.
go back to reference Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE, Metz HE, et al. Neutrophil elastase-mediated degradation of irs-1 accelerates lung tumor growth. Nat Med. 2010;16:219–23.CrossRefPubMedPubMedCentral Houghton AM, Rzymkiewicz DM, Ji H, Gregory AD, Egea EE, Metz HE, et al. Neutrophil elastase-mediated degradation of irs-1 accelerates lung tumor growth. Nat Med. 2010;16:219–23.CrossRefPubMedPubMedCentral
12.
go back to reference Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998;85:1457–9.CrossRefPubMed Siewert JR, Stein HJ. Classification of adenocarcinoma of the oesophagogastric junction. Br J Surg. 1998;85:1457–9.CrossRefPubMed
13.
go back to reference Wang LG, Ni Y, Su BH, Mu XR, Shen HC, Du JJ. MicroRNA-34b functions as a tumor suppressor and acts as a nodal point in the feedback loop with Met. Int J Oncol. 2013;42:957–62.PubMed Wang LG, Ni Y, Su BH, Mu XR, Shen HC, Du JJ. MicroRNA-34b functions as a tumor suppressor and acts as a nodal point in the feedback loop with Met. Int J Oncol. 2013;42:957–62.PubMed
14.
go back to reference Piccard H, Muschel RJ, Opdenakker G. On the dual roles and polarized phenotypes of neutrophils in tumor development and progression. Crit Rev Oncol/Hematol. 2012;82:296–309.CrossRef Piccard H, Muschel RJ, Opdenakker G. On the dual roles and polarized phenotypes of neutrophils in tumor development and progression. Crit Rev Oncol/Hematol. 2012;82:296–309.CrossRef
15.
go back to reference Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.CrossRefPubMedPubMedCentral Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G, Ling L, et al. Polarization of tumor-associated neutrophil phenotype by TGF-beta: “N1” versus “N2” TAN. Cancer Cell. 2009;16:183–94.CrossRefPubMedPubMedCentral
16.
go back to reference Shen M, Hu P, Donskov F, Wang G, Liu Q, Du J. Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis. PLoS One. 2014;9:e98259.CrossRefPubMedPubMedCentral Shen M, Hu P, Donskov F, Wang G, Liu Q, Du J. Tumor-associated neutrophils as a new prognostic factor in cancer: a systematic review and meta-analysis. PLoS One. 2014;9:e98259.CrossRefPubMedPubMedCentral
17.
go back to reference Wang J, Jia Y, Wang N, Zhang X, Tan B, Zhang G, et al. The clinical significance of tumor-infiltrating neutrophils and neutrophil-to-CD8+ lymphocyte ratio in patients with resectable esophageal squamous cell carcinoma. J Transl Med. 2014;12:7.CrossRefPubMedPubMedCentral Wang J, Jia Y, Wang N, Zhang X, Tan B, Zhang G, et al. The clinical significance of tumor-infiltrating neutrophils and neutrophil-to-CD8+ lymphocyte ratio in patients with resectable esophageal squamous cell carcinoma. J Transl Med. 2014;12:7.CrossRefPubMedPubMedCentral
18.
go back to reference Caruso RA, Bellocco R, Pagano M, Bertoli G, Rigoli L, Inferrera C. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy. Mod Pathol. 2002;15:831–7.CrossRefPubMed Caruso RA, Bellocco R, Pagano M, Bertoli G, Rigoli L, Inferrera C. Prognostic value of intratumoral neutrophils in advanced gastric carcinoma in a high-risk area in northern Italy. Mod Pathol. 2002;15:831–7.CrossRefPubMed
19.
go back to reference Zhao JJ, Pan K, Wang W, Chen JG, Wu YH, Lv L, et al. The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection. PLoS One. 2012;7:e33655.CrossRefPubMedPubMedCentral Zhao JJ, Pan K, Wang W, Chen JG, Wu YH, Lv L, et al. The prognostic value of tumor-infiltrating neutrophils in gastric adenocarcinoma after resection. PLoS One. 2012;7:e33655.CrossRefPubMedPubMedCentral
20.
go back to reference Skubitz KM, Campbell KD, Skubitz AP. CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils. J Leukoc Biol. 1996;60:106–17.PubMed Skubitz KM, Campbell KD, Skubitz AP. CD66a, CD66b, CD66c, and CD66d each independently stimulate neutrophils. J Leukoc Biol. 1996;60:106–17.PubMed
21.
go back to reference Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–31.CrossRefPubMed Murdoch C, Muthana M, Coffelt SB, Lewis CE. The role of myeloid cells in the promotion of tumour angiogenesis. Nat Rev Cancer. 2008;8:618–31.CrossRefPubMed
22.
go back to reference Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69:1553–60.CrossRefPubMedPubMedCentral Rodriguez PC, Ernstoff MS, Hernandez C, Atkins M, Zabaleta J, Sierra R, et al. Arginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytes. Cancer Res. 2009;69:1553–60.CrossRefPubMedPubMedCentral
23.
go back to reference Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS, et al. Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection. J Hepatol. 2011;54:497–505.CrossRefPubMed Li YW, Qiu SJ, Fan J, Zhou J, Gao Q, Xiao YS, et al. Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection. J Hepatol. 2011;54:497–505.CrossRefPubMed
24.
go back to reference Schaider H, Oka M, Bogenrieder T, Nesbit M, Satyamoorthy K, Berking C, et al. Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8. Int J Cancer. 2003;103:335–43.CrossRefPubMed Schaider H, Oka M, Bogenrieder T, Nesbit M, Satyamoorthy K, Berking C, et al. Differential response of primary and metastatic melanomas to neutrophils attracted by IL-8. Int J Cancer. 2003;103:335–43.CrossRefPubMed
25.
go back to reference Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120:1151–64.CrossRefPubMedPubMedCentral Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S. Neutrophils responsive to endogenous IFN-beta regulate tumor angiogenesis and growth in a mouse tumor model. J Clin Invest. 2010;120:1151–64.CrossRefPubMedPubMedCentral
26.
go back to reference Houghton AM. The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle. 2010;9:1732–7.CrossRefPubMed Houghton AM. The paradox of tumor-associated neutrophils: fueling tumor growth with cytotoxic substances. Cell Cycle. 2010;9:1732–7.CrossRefPubMed
27.
go back to reference Imai Y, Kubota Y, Yamamoto S, Tsuji K, Shimatani M, Shibatani N, et al. Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study. J Gastroenterol Hepatol. 2005;20:287–93.CrossRefPubMed Imai Y, Kubota Y, Yamamoto S, Tsuji K, Shimatani M, Shibatani N, et al. Neutrophils enhance invasion activity of human cholangiocellular carcinoma and hepatocellular carcinoma cells: an in vitro study. J Gastroenterol Hepatol. 2005;20:287–93.CrossRefPubMed
28.
go back to reference Grosse-Steffen T, Giese T, Giese N, Longerich T, Schirmacher P, Hansch GM, et al. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase. Clin Dev Immunol. 2012;2012:720768.CrossRefPubMedPubMedCentral Grosse-Steffen T, Giese T, Giese N, Longerich T, Schirmacher P, Hansch GM, et al. Epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma and pancreatic tumor cell lines: the role of neutrophils and neutrophil-derived elastase. Clin Dev Immunol. 2012;2012:720768.CrossRefPubMedPubMedCentral
29.
go back to reference Carus A, Ladekarl M, Hager H, Pilegaard H, Nielsen PS, Donskov F. Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome. Lung Cancer. 2013;81(1):130–7.CrossRefPubMed Carus A, Ladekarl M, Hager H, Pilegaard H, Nielsen PS, Donskov F. Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome. Lung Cancer. 2013;81(1):130–7.CrossRefPubMed
Metadata
Title
Tumor-infiltrating neutrophils predict poor outcome in adenocarcinoma of the esophagogastric junction
Authors
Pingping Hu
Zhaofei Pang
Hongchang Shen
Guanghui Wang
Haifeng Sun
Jiajun Du
Publication date
01-04-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 4/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-014-2927-4

Other articles of this Issue 4/2015

Tumor Biology 4/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine