Expression of CARD6, an NF-κB activator, in gastric, colorectal and oesophageal cancers

Aims: Activation of nuclear factor-kappa B (NF-κB) signalling is considered a crucial mechanism in the development of cancers. Caspase-associated recruitment domain 6 (CARD6) is a protein that activates NF-κB signalling evoked by RIP1, RIP2, Bcl-10 and MEKK.In this study, we analysed tissue expression of CARD6 protein in oesophageal squamous cell carcinoma (ESCC), gastric adenocarcinomas (GC) and colorectal adenocarcinomas (CRC). Methods: We analysed the expression of CARD6 protein in 58 ESCC, 100 GC and 103 CRC patients' tissues by immunohistochemistry using a tissue microarray (TMA) approach. Results: We found CARD6 immunostaining in cancer cells of ESCC (41/58; 70.7%), GC (45/100; 45.0%) and CRC (81/103; 78.6%). In the GC, intestinal-type GC (77.8%) showed higher expression of CARD6 than diffuse-type GC (20.0%) and mixed-type GC (50.0%). By contrast, corresponding normal epithelial cells of oesophagus (0%), stomach (8.0%) and colon (5.0%) displayed lower frequencies of CARD6 immunostaining. The CARD6 immunostaining was observed in nucleus/cytoplasm (ESCC) or cytoplasm (GC and CRC). The CARD6 expression was evident from an early TNM stage (stage I). Conclusion:The increased expression of CARD6 in ESCC, GC and CRC tissues compared to their corresponding normal cells suggested that neoexpression of CARD6 might be related to activation of NF-κB pathway in the cancers and might play a role in the development of most types of gastrointestinal cancers.