Department of Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-701, Korea.
Pathol Oncol Res. 2011 Mar;17(1):67-74. doi: 10.1007/s12253-010-9282-6. Epub 2010 Jun 4.
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.
癌胚抗原相关细胞黏附分子 1（CEACAM1）在整个肠道的上皮细胞中表达，是肿瘤细胞生长的负调节剂，这表明它可能作为肿瘤抑制因子发挥作用。在这项研究中，为了确定 CEACAM1 是否参与结直肠肿瘤发生，我们研究了 17 个结肠腺瘤和 123 例散发性结直肠癌中 CEACAM1 基因的遗传改变，包括突变和等位基因缺失。此外，还检测了 60 个结肠腺瘤和 123 例散发性结直肠腺癌中 CEACAM1 蛋白的表达模式。在结肠腺瘤中未发现突变，但在结直肠癌中检测到 4 个体细胞错义突变，L36F、T312I、V398I 和 A445V。有趣的是，所有这些突变都发生在具有临床 III 期的左侧结肠癌患者中。在 LOH 分析中，9 个腺瘤在至少一个标记物上具有信息性，其中 5 个（55.6%）显示等位基因缺失。38 个癌症在 D19S211 和 D19S872 标记物上具有信息性，其中 21 个（56.3%）在这些标记物上显示 LOH。统计学上，CEACAM1 基因座的等位基因缺失频率与临床病理参数无关（P > 0.05）。在免疫组织化学分析中，在 60 个结肠腺瘤和 123 个结直肠癌中，检测到 CEACAM1 蛋白表达缺失的有 9 个（15.0%）和 30 个（24.4%）。统计学上，CEACAM1 表达缺失与临床病理参数，包括临床分期、肿瘤部位、肿瘤大小、淋巴结转移和 5 年生存率无显著关系（P > 0.05）。这些数据表明，CEACAM1 的遗传改变和表达缺失可能有助于结直肠癌的发生，是早期事件。
