Skip to main content
Top
Published in: Clinical and Translational Oncology 9/2014

01-09-2014 | Research Article

Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal junction adenocarcinoma

Authors: H. Dong, L. Xie, C. Tang, S. Chen, Q. Liu, Q. Zhang, W. Zheng, Z. Zheng, H. Zhang

Published in: Clinical and Translational Oncology | Issue 9/2014

Login to get access

Abstract

Purpose

The poor prognosis of gastroesophageal junction (GEJ) adenocarcinoma is largely associated with metastasis. We here report the first study to investigate the expression of epithelial-mesenchymal transition (EMT) markers Snail1 and E-cadherin in GEJ adenocarcinoma.

Methods

Snail1 and E-cadherin were detected by immunohistochemistry in a cohort of 128 patients with surgically resected GEJ adenocarcinoma. We assessed the pathologic and prognostic relevance in all patients and within clinically different preserved E-cadherin and reduced E-cadherin-expressing sub-groups.

Results

Immunoreactivity for Snail1 and E-cadherin was positive in 68 and 43 % of tumors, respectively. Snail1-positive tumors had more frequent lymph node metastasis and advanced tumor stage. E-cadherin expression was highly associated with histological differentiation, tumor size, advanced stage, presence of lymph node metastasis and distant metastasis. Patients with positive E-cadherin expression or negative Snail1 expression had significantly favorable overall survival rate. In E-cadherin-preserved tumors, the expression of Snail1 was related to lymph node metastasis, advanced stage and poor patient outcome. However, Snail1 expression had no statistically significant relationship with clinicopathologic parameters or prognosis in the reduced E-cadherin-expressing sub-group. Multivariate survival analysis identified that tumor stage [hazard ratio (HR) 2.440; 95 % confidence interval (CI) 1.216–4.896; P = 0.012], lymph node metastasis (HR 2.404; 95 % CI 1.188–4.867; P = 0.015) and gender (HR 3.244; 95 % CI 1.568–6.714; P = 0.002) were independent prognostic markers for overall survival.

Conclusions

Snail1 may act more critically in E-cadherin-positive tumors. Evaluation of Snail1 and E-cadherin in GEJ adenocarcinoma may help in assessing malignant properties and stratifying patients.
Appendix
Available only for authorised users
Literature
1.
4.
go back to reference Nakamura M, Iwahashi M, Nakamori M, Naka T, Ojima T, Iida T, et al. Lower mediastinal lymph node metastasis is an independent survival factor of Siewert type II and III adenocarcinomas in the gastroesophageal junction. Am Surg. 2012;78(5):567–73.PubMed Nakamura M, Iwahashi M, Nakamori M, Naka T, Ojima T, Iida T, et al. Lower mediastinal lymph node metastasis is an independent survival factor of Siewert type II and III adenocarcinomas in the gastroesophageal junction. Am Surg. 2012;78(5):567–73.PubMed
7.
go back to reference Lagarde SM, ten Kate FJ, de Boer DJ, Busch OR, Obertop H, van Lanschot JJ. Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Am J Surg Pathol. 2006;30(2):171–6.PubMedCrossRef Lagarde SM, ten Kate FJ, de Boer DJ, Busch OR, Obertop H, van Lanschot JJ. Extracapsular lymph node involvement in node-positive patients with adenocarcinoma of the distal esophagus or gastroesophageal junction. Am J Surg Pathol. 2006;30(2):171–6.PubMedCrossRef
8.
go back to reference Gu Y, Swisher SG, Ajani JA, Correa AM, Hofstetter WL, Liao Z, et al. The number of lymph nodes with metastasis predicts survival in patients with esophageal or esophagogastric junction adenocarcinoma who receive preoperative chemoradiation. Cancer. 2006;106(5):1017–25. doi:10.1002/cncr.21693.PubMedCrossRef Gu Y, Swisher SG, Ajani JA, Correa AM, Hofstetter WL, Liao Z, et al. The number of lymph nodes with metastasis predicts survival in patients with esophageal or esophagogastric junction adenocarcinoma who receive preoperative chemoradiation. Cancer. 2006;106(5):1017–25. doi:10.​1002/​cncr.​21693.PubMedCrossRef
9.
go back to reference Matsumoto M, Natsugoe S, Nakashima S, Sakamoto F, Okumura H, Sakita H, et al. Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma. Cancer Lett. 2000;153(1–2):189–97.PubMedCrossRef Matsumoto M, Natsugoe S, Nakashima S, Sakamoto F, Okumura H, Sakita H, et al. Clinical significance of lymph node micrometastasis of pN0 esophageal squamous cell carcinoma. Cancer Lett. 2000;153(1–2):189–97.PubMedCrossRef
11.
go back to reference Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002;21(20):3241–6. doi:10.1038/sj.onc.1205416.PubMedCrossRef Blanco MJ, Moreno-Bueno G, Sarrio D, Locascio A, Cano A, Palacios J, et al. Correlation of Snail expression with histological grade and lymph node status in breast carcinomas. Oncogene. 2002;21(20):3241–6. doi:10.​1038/​sj.​onc.​1205416.PubMedCrossRef
12.
go back to reference Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–9. doi:10.1002/cncr.25537.PubMedCrossRef Sobin LH, Compton CC. TNM seventh edition: what’s new, what’s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer. 2010;116(22):5336–9. doi:10.​1002/​cncr.​25537.PubMedCrossRef
14.
go back to reference Natsugoe S, Uchikado Y, Okumura H, Matsumoto M, Setoyama T, Tamotsu K, et al. Snail plays a key role in E-cadherin-preserved esophageal squamous cell carcinoma. Oncol Rep. 2007;17(3):517–23.PubMed Natsugoe S, Uchikado Y, Okumura H, Matsumoto M, Setoyama T, Tamotsu K, et al. Snail plays a key role in E-cadherin-preserved esophageal squamous cell carcinoma. Oncol Rep. 2007;17(3):517–23.PubMed
15.
go back to reference Uchikado Y, Okumura H, Ishigami S, Setoyama T, Matsumoto M, Owaki T, et al. Increased Slug and decreased E-cadherin expression is related to poor prognosis in patients with gastric cancer. Gastric cancer: Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2011;14(1):41–9. doi:10.1007/s10120-011-0004-x.CrossRef Uchikado Y, Okumura H, Ishigami S, Setoyama T, Matsumoto M, Owaki T, et al. Increased Slug and decreased E-cadherin expression is related to poor prognosis in patients with gastric cancer. Gastric cancer: Off J Int Gastric Cancer Assoc Jpn Gastric Cancer Assoc. 2011;14(1):41–9. doi:10.​1007/​s10120-011-0004-x.CrossRef
18.
go back to reference Stanculescu D, Margaritescu C, Stepan A, Mitrut AO. E-cadherin in gastric carcinomas related to histological prognostic parameters. Rom J Morphol Embryology = Revue Roumaine de Morphologie et Embryologie. 2011;52(3 Suppl):1107–12. Stanculescu D, Margaritescu C, Stepan A, Mitrut AO. E-cadherin in gastric carcinomas related to histological prognostic parameters. Rom J Morphol Embryology = Revue Roumaine de Morphologie et Embryologie. 2011;52(3 Suppl):1107–12.
20.
go back to reference Wang ZS, Shen Y, Li X, Zhou CZ, Wen YG, Jin YB, et al. Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. 2013;. doi:10.1007/s13277-013-1185-1. Wang ZS, Shen Y, Li X, Zhou CZ, Wen YG, Jin YB, et al. Significance and prognostic value of Gli-1 and Snail/E-cadherin expression in progressive gastric cancer. Tumour Biol: J Int Soc Oncodevelopmental Biol Med. 2013;. doi:10.​1007/​s13277-013-1185-1.
21.
go back to reference Rosivatz E, Becker KF, Kremmer E, Schott C, Blechschmidt K, Hofler H, et al. Expression and nuclear localization of Snail, an E-cadherin repressor, in adenocarcinomas of the upper gastrointestinal tract. Virchows Arch: Int J Pathol. 2006;448(3):277–87. doi:10.1007/s00428-005-0118-9.CrossRef Rosivatz E, Becker KF, Kremmer E, Schott C, Blechschmidt K, Hofler H, et al. Expression and nuclear localization of Snail, an E-cadherin repressor, in adenocarcinomas of the upper gastrointestinal tract. Virchows Arch: Int J Pathol. 2006;448(3):277–87. doi:10.​1007/​s00428-005-0118-9.CrossRef
22.
go back to reference Li SL, Gao DL, Zhao ZH, Liu ZW, Zhao QM, Yu JX, et al. Correlation of matrix metalloproteinase suppressor genes RECK, VEGF, and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma. WJG. 2007;13(45):6076–81.PubMedCrossRef Li SL, Gao DL, Zhao ZH, Liu ZW, Zhao QM, Yu JX, et al. Correlation of matrix metalloproteinase suppressor genes RECK, VEGF, and CD105 with angiogenesis and biological behavior in esophageal squamous cell carcinoma. WJG. 2007;13(45):6076–81.PubMedCrossRef
23.
go back to reference Sung CO, Park CK, Kim SH. Classification of epithelial-mesenchymal transition phenotypes in esophageal squamous cell carcinoma is strongly associated with patient prognosis. Mod Pathol: Off J U. S. Can Acad Pathol, Inc. 2011;24(8):1060–8. doi:10.1038/modpathol.2011.59.CrossRef Sung CO, Park CK, Kim SH. Classification of epithelial-mesenchymal transition phenotypes in esophageal squamous cell carcinoma is strongly associated with patient prognosis. Mod Pathol: Off J U. S. Can Acad Pathol, Inc. 2011;24(8):1060–8. doi:10.​1038/​modpathol.​2011.​59.CrossRef
24.
go back to reference Barbera MJ, Puig I, Dominguez D, Julien-Grille S, Guaita-Esteruelas S, Peiro S, et al. Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene. 2004;23(44):7345–54. doi:10.1038/sj.onc.1207990.PubMedCrossRef Barbera MJ, Puig I, Dominguez D, Julien-Grille S, Guaita-Esteruelas S, Peiro S, et al. Regulation of Snail transcription during epithelial to mesenchymal transition of tumor cells. Oncogene. 2004;23(44):7345–54. doi:10.​1038/​sj.​onc.​1207990.PubMedCrossRef
25.
go back to reference Guo HM, Zhang XQ, Xu CH, Zou XP. Inhibition of invasion and metastasis of gastric cancer cells through snail targeting artificial microRNA interference. Asian Pac J Cancer Prev: APJCP. 2011;12(12):3433–8.PubMed Guo HM, Zhang XQ, Xu CH, Zou XP. Inhibition of invasion and metastasis of gastric cancer cells through snail targeting artificial microRNA interference. Asian Pac J Cancer Prev: APJCP. 2011;12(12):3433–8.PubMed
26.
go back to reference Castro Alves C, Rosivatz E, Schott C, Hollweck R, Becker I, Sarbia M, et al. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. J Pathol. 2007;211(5):507–15. doi:10.1002/path.2138.PubMedCrossRef Castro Alves C, Rosivatz E, Schott C, Hollweck R, Becker I, Sarbia M, et al. Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin. J Pathol. 2007;211(5):507–15. doi:10.​1002/​path.​2138.PubMedCrossRef
29.
go back to reference Roy HK, Iversen P, Hart J, Liu Y, Koetsier JL, Kim Y, et al. Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: modulation of apoptosis, proliferation, and fractal dimension. Mol Cancer Ther. 2004;3(9):1159–65.PubMed Roy HK, Iversen P, Hart J, Liu Y, Koetsier JL, Kim Y, et al. Down-regulation of SNAIL suppresses MIN mouse tumorigenesis: modulation of apoptosis, proliferation, and fractal dimension. Mol Cancer Ther. 2004;3(9):1159–65.PubMed
Metadata
Title
Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal junction adenocarcinoma
Authors
H. Dong
L. Xie
C. Tang
S. Chen
Q. Liu
Q. Zhang
W. Zheng
Z. Zheng
H. Zhang
Publication date
01-09-2014
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 9/2014
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-013-1149-3

Other articles of this Issue 9/2014

Clinical and Translational Oncology 9/2014 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