Significance of Twist expression and its association with E-cadherin in esophageal squamous cell carcinoma

Abstract

Background: Twist is a basic helix-loop-helix (bHLH) transcriptional factor that has been identified to play an important role in epithelial-mesenchymal transition (EMT)-mediated metastasis through the regulation of E-cadherin expression. However, few authors have examined the expression of Twist and E-cadherin and their prognostic value in patients with esophageal squamous cell carcinoma (ESCC). The purpose of this study is to evaluate the clinical significance of Twist and E-cadherin expression in ESCC.

Methods: We immunohistochemically investigated the relationship between their expression and clinicopathological factors including prognosis in surgical specimens of primary tumors in 166 patients with ESCC.

Results: The expression rate of high Twist was 42.0% and that of preserved E-cadherin was 40.4%. The expression of high Twist and reduced E-cadherin was significantly associated with depth of tumor invasion, lymph node metastasis, distant nodal metastasis, stage and lymphatic invasion, and poor prognosis. High Twist expression significantly correlated with reduced E-cadherin expression. In the preserved E-cadherin group, the 5-year survival rate was better for patients who were low for Twist expression than for those who were high for Twist expression. Multivariate analysis indicated that the combination of low Twist and preserved E-cadherin expression was an independent prognostic factor along with tumor depth, distant nodal metastasis and E-cadherin expression.

Conclusions: Evaluation of Twist and E-cadherin expressions should be useful for determining tumor properties, including prognosis, in patients with ESCC.

Figure 1

Expression of Twist and E-cadherin proteins in ESCCs. (A) High expression of Twist. (B) Weak expression of Twist. (C) Negative expression of Twist. (D) Preserved expression of E-cadherin is detected in the cancer adjacent normal tissue. (E) Preserved expression of E-cadherin. (F) Reduced expression of E-cadherin (Original magnification, ×400).

Figure 2

The postoperative 5-year survival curve of patients according to the expression of Twist (A) and E-cadherin (B) proteins. There was a significant difference in survival between the patients with high and low expressions of Twist (P = 0.0014). There was also a significant difference in survival between the patients with preserved and reduced expressions of E-cadherin (P = 0.0007).

Figure 3

The postoperative 5-year survival curves between the patients with high Twist or low Twist expression according to E-cadherin expressions. (A) In the preserved E-cadherin group, the patients with low Twist expression had a better outcome than those with high Twist expression (P = 0.0099). (B) In the reduced E-cadherin group, the survival curve was not significantly different according to the Twist expression (P = 0.25).

Figure 4

The postoperative 5-year survival curves according to combined expression of Twist and E-cadherin. Five-year survival rate of patients with both low Twist and preserved E-cadherin expression had a significant better outcome than those with the other groups.