Background: MUC4 is a membrane mucin protein which is secreted from various organs of the gastrointestinal system including pancreas and gallbladder. Recent studies suggest that MUC4 is a novel intramembrane ligand for receptor tyrosine kinase ErbB2 (Her2/Neu), and expression of MUC4 has been implicated as a marker for diagnosis and progression of pancreatic adenocarcinomas and cholangiocarcinomas. However, the expression level of MUC4 and its roles in colon carcinoma is not well understood. Aims: To investigate the expression of MUC4 and ErbB2 in human colon carcinomas at various stages of progression. Methods: The specimens from 138 cases of colon adenomas and carcinomas (20 adenomas; pTis 12; pT1/2 33; pT3 64; pT4 9 carcinomas) were used for this study. Immunohistochemical analysis was performed using mAb for MUC4 and ErbB2. We defined MUC4 positive as more than 10% of all cancerous glands staining positive. The expression of ErbB2 was classified as 1+, 2+ and 3+, based on intensity of staining. Confocal laser scanning microscopy (CLSM) was used to confirm co-localization of MUC4 and ErbB2. Results: MUC4 staining was observed in 60% of epithelia of adenomas and 26% of those of carcinomas. ErbB2 protein was expressed in 40% of adenomas and 100% of carcinomas (Table). However, no stainings of MUC4 and ErbB2 were observed in epithelia of the adjacent non-cancerous tissues. The results of CLSM revealed that the MUC4 and ErbB2 were partially co-localized at the apical site of cancerous epithelia. Conclusions: The expression of MUC4 protein was observed in adenomas and early stages of carcinomas, and the expression rate decreased along with tumor progression. The results suggest that MUC4 may play an important role for colon carcinogenesis possibly through potentiating ErbB2 signal pathways.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]