Overexpression of the Snail gene transcriptional repressor promotes an epithelial-to-mesenchymal transition (EMT) in epithelial tumor cell lines. In this study, we aimed to determine the correlation between Snail protein expression and clinicopathological features and to test whether Snail can be used as a marker to distinguish gastric carcinomas from benign tissues in biopsy samples. The results of immunohistochemistry with an antibody against Snail showed that most adenocarcinomas had positive Snail expression, whereas weak Snail expression was detected in a small number of gastritis and gastric adenomas. Snail-positive cells were detected in the stroma as well as in the glandular epithelium in some adenocarcinomas. In addition to Snail immunostaining, immunostaining of the EMT-related molecules, E-cadherin and vimentin, was performed. E-cadherin was not detected in adenocarcinomas that expressed Snail, whereas gastritis and adenomas stained positively for E-cadherin. Vimentin expression was seen in adenocarcinomas with positive Snail expression, whereas gastritis and adenomas did not express vimentin. In conclusion, we propose that Snail is a useful biomarker to distinguish gastric adenocarcinomas from benign lesions in biopsy samples. 1. Introduction The transcription factor Snail is a zinc finger protein that represses transcription of the E-cadherin gene through an interaction of the Snail COOH-terminal region with a 5′-CACCTG-3′ sequence called the E-box in the E-cadherin promoter region [1]. The loss of E-cadherin expression has been shown to be responsible for the loss of cell-cell adhesion and cell polarity that occurs during the early stages of invasion and metastasis of carcinoma cells [1]. During the process of tumor invasion, tumor cells lose their properties of cell-cell adhesion and frequently undergo profound changes in their phenotype known as epithelial-to-mesenchymal transition (EMT) [2]. Snail is one of the most important regulators of EMT [3]. Gastric cancer is the most common malignant tumor in Japan. In 1998, more than 100,000 new cases were reported. By 2015, it is anticipated that this number will climb to nearly 150,000 [4]. The only potentially curative treatment for gastric cancer is surgical resection of all gross and microscopic disease. Deciding which type of surgery to perform is one of the most important surgical issues in this disease. Recent advances in endoscopy have allowed easy exploration of the stomach by gastroenterologists. However, the final diagnosis of gastric cancer and the definitive treatment still
References
[1]
A. Cano, M. A. Pérez-Moreno, I. Rodrigo et al., “The transcription factor Snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression,” Nature Cell Biology, vol. 2, no. 2, pp. 76–83, 2000.
[2]
C. Franci, M. Gallen, F. Alameda et al., “Snail1 protein in the stroma as a new putative prognosis marker for colon tumours,” PLoS ONE, vol. 4, no. 5, Article ID e5595, 2009.
[3]
K. F. Becker, E. Rosivatz, K. Blechschmidt, E. Kremmer, M. Sarbia, and H. H？fler, “Analysis of the E-cadherin repressor snail in primary human cancers,” Cells Tissues Organs, vol. 185, no. 1–3, pp. 204–212, 2007.
[4]
M. Fujii, M. Kochi, and T. Takayama, “Recent advances in chemotherapy for advanced gastric cancer in Japan,” Surgery Today, vol. 40, no. 4, pp. 295–300, 2010.
[5]
D. Y. Graham, M. Kato, and M. Asaka, “Gastric endoscopy in the 21st century: appropriate use of an invasive procedure in the era of non-invasive testing,” Digestive and Liver Disease, vol. 40, no. 7, pp. 497–503, 2008.
[6]
C. Castro Alves, E. Rosivatz, C. Schott et al., “Slug is overexpressed in gastric carcinomas and may act synergistically with SIPI and Snail in the down-regulation of E-cadherin,” Journal of Pathology, vol. 211, no. 5, pp. 507–515, 2007.
[7]
T. Sano and Y. Kodera, “Japanese gastric cancer treatment guidelines 2010 (ver. 3),” Gastric Cancer, vol. 14, no. 2, pp. 113–123, 2011.
[8]
R. Nishioka, S. Itoh, T. Gui et al., “SNAIL induces epithelial-to-mesenchymal transition in a human pancreatic cancer cell line (BxPC3) and promotes distant metastasis and invasiveness in vivo,” Experimental and Molecular Pathology, vol. 89, no. 2, pp. 149–157, 2010.
[9]
E. Rosivatz, I. Becker, K. Specht et al., “Differential expression of the epithelial-mesenchymal transition regulators Snail, SIP1, and twist in gastric cancer,” American Journal of Pathology, vol. 161, no. 5, pp. 1881–1891, 2002.
[10]
C. Pena, J. M. Garcia, M. J. Larriba et al., “SNAI1 expression in colon cancer related with CDH1 and VDR downregulation in normal adjacent tissue,” Oncogene, vol. 28, no. 49, pp. 4375–4385, 2009.
[11]
K. Vuoriluoto, H. Haugen, S. Kiviluoto et al., “Vimentin regulates EMT induction by Slug and oncogenic H-Ras and migration by governing Axl expression in breast cancer,” Oncogene, vol. 30, no. 12, pp. 1436–1448, 2011.
[12]
K. Takemura, R. Hirayama, K. Hirokawa et al., “Expression of vimentin in gastric cancer: a possible indicator for prognosis,” Pathobiology, vol. 62, no. 3, pp. 149–154, 1994.
[13]
M. Asaka, M. Kato, and D. Y. Graham, “Strategy for eliminating gastric cancer in Japan,” Helicobacter, vol. 15, no. 6, pp. 486–490, 2010.
[14]
T. Aoyama, T. Yoshikawa, T. Watanabe et al., “Macroscopic tumor size as an independent prognostic factor for stage II/III gastric cancer patients who underwent D2 gastrectomy followed by adjuvant chemotherapy with S-1,” Gastric Cancer, vol. 14, no. 3, pp. 274–278, 2011.
[15]
N. Kaibara, Y. Otani, H. Inoue et al., “Meeting report of the 76th Congress of the Japanese Gastric Cancer Association,” Gastric Cancer, vol. 7, no. 4, pp. 185–195, 2004.
[16]
T. Foukakis, L. Lundell, M. Gubanski, and P. A. Lind, “Advances in the treatment of patients with gastric adenocarcinoma,” Acta Oncologica, vol. 46, no. 3, pp. 277–285, 2007.
[17]
M. A. Kim, H. S. Lee, H. E. Lee, J. H. Kim, H. K. Yang, and W. H. Kim, “Prognostic importance of epithelial-mesenchymal transition-related protein expression in gastric carcinoma,” Histopathology, vol. 54, no. 4, pp. 442–451, 2009.
[18]
Y. Usami, S. Satake, F. Nakayama et al., “Snail-associated epithelial-mesenchymal transition promotes oesophageal squamous cell carcinoma motility and progression,” Journal of Pathology, vol. 215, no. 3, pp. 330–339, 2008.
