Clinicopathological significance of expression of p-c-Jun, TCF4 and beta-Catenin in colorectal tumors

BACKGROUND: A recent study has shown that phosphorylated c-Jun (p-c-Jun) interacts with TCF4 to form a complex that cooperatively enhances their transcriptional activity in the presence of β-Catenin, and that their interaction is critical for mouse intestinal tumorigenesis. To determine the significance of these three proteins in human colorectal tumors, we analyzed their nuclear expression by immunohistochemistry. METHODS: we analyzed their nuclear expression by immunohistochemistry using paraffin-embedded specimens of 68 resected colorectal tumors, which consisted of 19 adenomas, 14 high-grade intraepithelial neoplasia (HGINs) and 35 adenocarcinomas. We also analyzed the expression of MMP7, which has functional AP-1 and TCF binding sites in its promoter. RESULTS: Expression of p-c-Jun, TCF4 and β-Catenin were significantly higher in adenomas than in the adjacent normal epithelia. Expression of p-c-Jun and β-Catenin in HGINs and adenocarcinomas were also significantly higher than in the adjacent normal epithelia. p-c-Jun expression, but not TCF4 and β-Catenin, was higher in adenomas and HGINs than in adenocarcinomas, in which p-c-Jun expression was negatively correlated with pT stage progression. Furthermore, significant correlations of expression were observed between p-c-Jun and TCF4 (r = 0.25, p = 0.04), TCF4 and β-Catenin (r = 0.30, p = 0.01), p-c-Jun and MMP7 (r = 0.26, p = 0.03), and TCF4 and MMP7 (r = 0.39, p = 0.0008), respectively. CONCLUSION: These results suggest that nuclear expression of p-c-Jun, TCF4 and β-Catenin have important roles in human colorectal tumor development and that p-c-Jun may play a pivotal role in the earlier stages of tumor development.