Journal
HUMAN PATHOLOGY
Volume 44, Issue 2, Pages 173-180Publisher
W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.humpath.2012.03.029
Keywords
Colorectal cancer; EMT; Lymph node metastasis; Metastasis; Snail; Twist
Categories
Funding
- National Natural Science Foundation of China [81172040, 81072042, 81001086, 81000934]
- Medical Scientific Research Foundation of Guangdong Province [WSTJJ20091225142431198101210628]
- Project for Outstanding Young and Creative Talent Training Plan in Higher Education Institutions of Guangdong Province [LYM10010]
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Snail and Twist, transcriptional repressors of E-cadherin as well as inducers of epithelial-mesenchymal transition, play pivotal roles in tumor invasion and metastasis. We investigated the expression of Snail, Twist, and E-cadherin by immunohistochemistry in 193 colorectal cancers, including 79 with positive lymph nodes, 36 with tumor deposits, 39 with both, and 39 with no metastases. Snail was expressed to a greater extent in the group with positive lymph nodes (68.4%), whereas Twist was overexpressed in patients with other metastases (75.0%). Ectopic expression of Snail and Twist correlated with reduced membranous expression of E-cadherin. Importantly, Snail overexpression correlated significantly with lymph node metastasis (P < .0001), whereas Twist up-regulation correlated strongly with other metastases (P < .0001). Multivariate logistic regression analysis showed that Snail was an independent predictor of lymph node metastasis (odds ratio, 4.445; 95% confidence interval, 2.250-8.781; P < .0001 ), whereas Twist displayed predictive value for metastasis formation (odds ratio, 5.606; 95% confidence interval, 2.829-11.111; P < .0001), suggesting that lymph node and other metastases may follow different signaling pathways. In conclusion, ectopic expression of Snail and Twist contributed to lymph node and disseminated metastasis, respectively, by reducing E-cadherin expression, providing a novel role for Snail and Twist in the progression of colorectal cancer. (c) 2013 Elsevier Inc. All rights reserved.
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