Carcinoembryonic antigen family members CEACAM6 and CEACAM7 are differentially expressed in normal tissues and oppositely deregulated in hyperplastic colorectal polyps and early adenomas

Four members of the carcinoembryonic antigen (CEA) family, CEA, CEACAM1 (BGP), CEACAM6 (NCA-50/90), and CEACAM7 (CGM2), are coexpressed in normal colorectal epithelia but are deregulated in colorectal cancers, where they could play a role in tumorigenesis. As a basis for functional studies, their expression patterns in normal tissues first need to be clarified. This is well documented for CEACAM1 and CEA but not for CEACAM6 or CEACAM7, We have now carried out immunohistochemical expression studies on 35 different organs, using CEACAM6-specific (9A6) and CEACAM7-specific (BAC2) monoclonal antibodies. CEACAM7 was only found on the apical surface of highly differentiated epithelial cells in the colorectal mucosa and on isolated ductal epithelial cells within the pancreas, CEACAM6 was expressed in granulocytes and epithelia from various organs. CEACAM6 and CEACAM7 expression correlated with apoptosis at the table region of the normal colon, and both were absent from highly proliferating cells at the base of colonic crypts, CEACAM6 revealed a broader expression zone in proliferating cells in hyperplastic polyps and adenomas compared with normal mucosa, whereas CEACAM7 was completely absent, Down-regulation of CEACAM7 and up-regulation of CEACAM6 expression in hyperplastic polyps and early adenomas represent some of the earliest observable molecular events leading to colorectal tumors.