Expression and association of CD44v6 with prognosis in T2-3N0M0 esophageal squamous cell carcinoma

Abstract

Aim: To investigate the expression of CD44v6 in stage T2-3N0M0 esophageal squamous cell carcinoma (ESCC) and its prognostic significance.

Methods: The expression of CD44v6 in a series of 227 ESCC specimens was evaluated by immunohistochemistry (IHC). A reproducible semiquantitative method which took both staining percentage and intensity into account was applied for IHC scoring, and receiver operating characteristic (ROC) curve analysis was utilized to select the cut-off score for high or low IHC reactivity. Then, the correlations of CD44v6 expression with clinicopathological features of patients and its prognostic relevance were determined.

Results: In the present study, the proportion of low CD44v6 expression was found significantly lower in Grade 3 of ESCC, than that of Grade 1 and Grade 2 of ESCC. There are no significant correlations between CD44v6 expression and other clinicopathological parameters including gender, age, tumor size, tumor location, depth of invasion and pathological stage. The Kaplan-Meier survival curves showed that up-regulated expression of CD44v6 indicated a poorer post-operative survival for ESCC patients of stage T2-3N0M0 (P=0.009), especially for those with T2 lesions (P=0.044) or with stage IIB diseases (P=0.005). Multivariate analysis also confirmed that CD44v6 expression [relative risk, 1.639; 95% confidence interval (CI): 1.142-2.354, P=0.007] and depth of invasion (relative risk, 1.487; 95% CI: 1.063-2.080, P=0.020) were independent prognostic factors.

Conclusions: Elevated CD44v6 expression may be an adverse prognostic indicator for patients with stage T2-3N0M0 ESCC, especially for those with T2 lesions or stage IIB diseases.

Keywords: CD44v6; Esophageal squamous cell carcinoma (ESCC); immunohistochemistry (IHC); prognosis; receiver operating characteristic curve.

Figure 1

Expression of CD44v6 in esophageal squamous cell carcinoma (ESCC) tissue (Envision, ×400). (A) Immunohistochemical staining of CD44v6 in cytoplasm and membrane (IHC score: 15); (B) Immunohistochemical staining of CD44v6 in cytoplasm (IHC score: 3). IHC, immunohistochemistry.

Figure 2

Receiver operating characteristic (ROC) curve analysis for CD44v6 and the selection of cut-off score.

Figure 3

Kaplan-Meier survival function for patients with T2-3N0M0 esophageal squamous cell carcinoma (ESCC) according to CD44v6 expression.

Figure 4

Kaplan-Meier survival curves for patients with esophageal squamous cell carcinoma (ESCC) stratified for depth of invasion according to CD44v6 expression. (A) Correlation between CD44v6 expression and post-operative survival of patients with T2 lesions; (B) Correlation between CD44v6 expression and post-operative survival of patients with T3 lesions.

Figure 5

Kaplan-Meier survival curves for patients with esophageal squamous cell carcinoma (ESCC) stratified for pathological stage according to CD44v6 expression. (A) Correlation between CD44v6 expression and post-operative survival of patients with IIA diseases; (B) Correlation between CD44v6 expression and post-operative survival of patients with IIB diseases.