BACKGROUND AND OBJECTIVES: Transcription factor 3 (TCF3) implicates Wnt 
signaling pathway and regulates E-cadherin expression, which is involved in 
aggressiveness of tumors. This study aims to investigate the role of TCF3 in 
predicting prognosis of patients with stage II and III colorectal cancer (CRC).
METHODS: Real-Time quantitative PCR was performed in 64 fresh CRC tissues and 6 
cell lines to examine TCF3 mRNA expression. TCF3 protein expression dynamics 
were detected by immunohistochemistry of 118 paraffin-embedded specimens, and 
the clinical significance of TCF3 was assessed by clinical correlation and 
Kaplan-Meier analyses. Aberrant hypomethylation of TCF3 promoter was also 
investigated using bisulfite sequencing and methylation specific PCR.
RESULTS: The up-regulation of TCF3 mRNA was frequently detected both in CRC 
tissues with recurrence and metastasis-derived cell lines. The expression level 
of TCF3 protein was significantly correlated with histological type (P = 0.038) 
and disease-free survival time (P = 0.002). Higher TCF3 expression indicated 
poor prognostic outcomes (P<0.05, log-rank test). Multivariate analysis also 
showed strong TCF3 protein expression and perineural invasion were independent 
adverse prognosticators in CRC (P = 0.010, 0.000). Moreover, it was showed that 
promoter hypomethylation of TCF3 is associated with its up-expression.
CONCLUSIONS: This study highlighted the prognostic value of TCF3 in stage II and 
III CRC. The up-regulation of TCF3, which is mainly caused by promoter 
hypomethylation, is one of the molecular mechanisms involved in the development 
and progression of CRC.