The influence of metastatic site on the expression of CEA and cellular localization of β-catenin in colorectal cancer.

Background and Aim: The usefulness of carcinoembryonic antigen (CEA) in the diagnosis and prognosis of colorectal cancer (CRC) is unclear. The aim was to analyze changes in the expression of CEA during CRC progression and metastasis, so as to determine the influence of tumor metastatic organ on the CEA expression by CRC cells. Methods: The human biopsies of adenocarcinomas in colon and CRC liver and lung metastases were analyzed by immunohistochemistry for the expression of CEA. Expression of E-cadherin and beta-catenin was also analyzed to localize the CRC neoplastic glands in metastatic tissues. Results: The CRC neoplastic glands in colon and liver expressed significantly higher amount of CEA compared with crypts in normal colon. In contrast, CRC neoplastic glands formed in lung expressed low CEA level. However, CEA expression was high in areas of tumor necrosis in lung. E-cadherin and beta-catenin were cell membrane-bound in normal crypts and CRC neoplastic glands in colon and liver. Although these two proteins were also cell membrane-bound in a majority of CRC neoplastic glands in lungs, a significant proportion of these expressed beta-catenin in the nucleus, which lacked either E-cadherin or beta-catenin at the cell membrane. Conclusion: Our findings indicate that lung microenvironment is unique in that it suppresses the expression of CEA by CRC cells forming neoplastic glands. In addition, lung microenvironment promotes nuclear localization of beta-catenin, suggesting that the Wnt signaling pathway is relatively active highly in CRC metastasized to lung, when compared with liver or colon.