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

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.