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.