Snail1 correlates with patient outcomes in E-cadherin-preserved gastroesophageal junction adenocarcinoma
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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.
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.
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.
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.
KeywordsSnail1 E-cadherin Epithelial-mesenchymal transition Gastroesophageal junction adenocarcinoma
This work was supported in part by National Natural Science Foundation of China grants 30973508, 81071736 (H. Zhang) and 81171994 (L. Xie); Fund for University Students Innovation Program of Guangdong Province 1056010001 (W. Zheng).
Conflict of interest
No potential conflicts of interest are disclosed.
- 5.Maeda H, Okabayashi T, Nishimori I, Sugimoto T, Namikawa T, Dabanaka K, et al. Clinicopathologic features of adenocarcinoma at the gastric cardia: is it different from distal cancer of the stomach? J Am Coll Surg. 2008;206(2):306–10. doi: 10.1016/j.jamcollsurg.2007.06.306.PubMedCrossRefGoogle Scholar
- 8.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.PubMedCrossRefGoogle Scholar
- 10.Yang Z, Zhang H, Kumar R. Regulation of E-cadherin. In: Breast Cancer Online. Cambridge University Press 2005. http://journals.cambridge.org/article_S1470903105003159.
- 15.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.CrossRefGoogle Scholar
- 18.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.Google Scholar
- 21.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.CrossRefGoogle Scholar