Differential expression of cyclo-oxygenase-2 and nuclear β-catenin in colorectal cancer tissue

Abstract

Summary

Background

Both adenomatous polyposis coli (APC) gene mutation and cyclo-oxygenase (COX)-2 are thought to play key roles in colorectal carcinogenesis. Nuclear accumulation of β-catenin results from APC gene mutation, which leads to enhanced transcription and activation of target genes, including cyclin D1. In vitro studies suggest that Cox-2 transcription is directly regulated by β-catenin/TCF complexes.

Aim

To investigate the relationship between cellular localization of β-catenin and COX-2 in colorectal cancer.

Methods

We performed immunohistochemical analysis of β-catenin, cyclin D1 and COX-2 expression in 50 resected colorectal cancer cases.

Results

The proportion of cases positive for cyclin D1 was higher in nuclear β-catenin-positive cases than in negative cases (P < 0.001). Serial sections revealed that the co-localization of cyclin D1 and nuclear β-catenin was most frequently evident in the tumour cells at the advancing margin of invasive carcinoma. Conversely, there was no association between COX-2 and nuclear β-catenin expression, either topographically or statistically. The staining patterns for COX-2 and nuclear β-catenin differed; COX-2 was diffuse and homogeneous, whereas nuclear β-catenin was focal and preferentially distributed at the invasive margin of cancer cells.

Conclusions

These two important modulators of colorectal tumourigenesis are differentially expressed. Cox-2 and β-catenin transcription may be activated by different pathways.