Genetic alterations and expression pattern of CEACAM1 in colorectal adenomas and cancers.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on epithelial cells throughout the intestinal tract and is a negative regulator of tumor cell growth, suggesting that it may function as a tumor suppressor. In this study, to determine whether the CEACAM1 is involved in colorectal tumorigenesis, we have investigated the genetic alterations, including mutations and allelic loss, of the CEACAM1 gene in 17 colonic adenomas and 123 sporadic colorectal cancers. In addition, the expression pattern of the CEACAM1 protein was examined in 60 colonic adenomas and 123 sporadic colorectal adenocarcinomas. No mutation was found in colonic adenomas, but four somatic missense mutations, L36F, T312I, V398I and A445V, were detected in colorectal cancers. Interestingly, all of the mutations were found in left-side colon cancers of the patients with clinical stage III. In LOH analysis, nine adenomas were informative for at least one of the markers and five (55.6%) showed allelic loss. Thirty-eight cancers were informative at D19S211 and D19S872 markers and 21 (56.3%) showed LOH at these markers. Statistically, the frequency of allelic loss at the CEACAM1 locus was not associated with clinicopathologic parameters (P > 0.05). In immunohistochemical analysis, loss of expression of CEACAM1 protein was detected in nine (15.0%) and 30 (24.4%) of 60 colorectal adenomas and 123 colorectal cancers. Statistically, there was no significant relationship between loss of CEACAM1 expression and clinicopathologic parameters, including clinical stage, tumor location, tumor size, lymph node metastasis and 5-year survival (P > 0.05). These data suggest that genetic alteration and loss of expression of the CEACAM1 may contribute to the development of colorectal cancers, as an early event.