Abstract
Background
The aim of our study was to analyze the expression and possible role of CD66a in colorectal adenoma and adenocarcinoma and the relationship between its expression and pre-operation serum carcinoembryonic antigen (CEA) level and tumor stage in patients with colorectal adenocarcinomas.
Methods
Paraffin-embedded sections from 184 patients including 42 colorectal adenomas with low-grade dysplasia, 43 adenomas with high-grade dysplasia, and 99 adenocarcinomas were collected for this study. Immunohistochemical analysis was performed, and the expression and the location of CD66a were evaluated and were correlated with β-catenin nuclear expression.
Results
The expression of CD66a was found not only in the apical membrane of neoplastic glands but also in secretion within the lumen of the neoplastic glands including adenomas and adenocarcinomas. Expressions of secreted CD66a were of higher level in adenocarcinoma than in adenoma with high-grade dysplasia and adenoma with low-grade dysplasia (p < 0.0001). High expression of secreted CD66a was also associated with tumor stage, invasion, and pre-operation serum CEA level of patients with colorectal adenocarcinoma.
Conclusions
This study implied that CD66a can function both as an epithelial cell adhesion protein or alternatively as secreted CD66a. In addition, a high expression of CD66a was significantly correlated with tumor invasion, stage, and pre-operation serum CEA level.
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References
Massimo P, Carina JV (1994) Adhesion molecules: novel molecular tools in tumor pathology. Human Pathol 25:849–856
Stoffel A, Neumaier M, Gaida FJ, Fenger U, Drzeniek Z, Haubeck HD, Wagener C (1993) Monoclonal, anti-domain and anti-peptide antibodies assign the molecular weight 160,000 granulocyte membrane antigen of the CD66 cluster to a mRNA species encoded by the biliary glycoprotein gene, a member of the carcinoembryonic antigen gene family. J Immunol 150:4978–4984
Kuijpers TW, Hoogerwerf M, van der Laan LJ, Nagel G, van der Schoot CE, Grunert F, Roos D (1992) CD66 nonspecific cross-reacting antigens are involved in neutrophil adherence to cytokine-activated endothelial cells. J Cell Biol 118:457–466
Hinoda Y, Neumaier M, Hefta SA, Drzeniek Z, Wagener C, Shively L, Hefta LJ, Shively JE, Paxton RJ (1988) Molecular cloning of a cDNA coding biliary glycoprotein I: primary structure of a glycoprotein immunologically crossreactive with carcinoembryonic antigen. Proc Natl Acad Sci USA 85:6959–6963
Odin P, Asplund M, Busch C, Obrink B (1988) Immunohistochemical localization of cellCAM 105 in rat tissues: appearance in epithelia, platelets, and granulocytes. J Histochem Cytochem 36:729–739
Svenberg T, Hammarstrom S, Hedin A (1979) Purification and properties of biliary glycoprotein I (BGP I). Immunochemical relationship to carcinoembryonic antigen. Mol Immunol 16:245–252
Prall F, Nollau P, Neumaier M, Haubeck HD, Drzeniek Z, Helmchen U, Loning T, Wagener C (1996) CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. J Histochem Cytochem 44:35–41
Neumaier M, Paululat S, Chan A, Matthaes P, Wagener C (1993) Biliary glycoprotein, a potential human cell adhesion molecule, is down-regulated in colorectal carcinomas. Proc Natl Acad Sci USA 90:10744–10748
Riethdorf L, Lisboa BW, Henkel U, Naumann M, Wagener C, Loning T (1997) Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland. J Histochem Cytochem 45:957–963
Bamberger AM, Riethdorf L, Nollau P, Naumann M, Erdmann I, Gotze J, Brummer J, Schulte HM Wagener C, Loning T (1998) Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer. Am J Pathol 152:1401–1406
Luo W, Tapolsky M, Earley K, Wood CG, Wilson DR, Logothetis CJ, Lin SH (1999) Tumor-suppressive activity of CD66a in prostate cancer. Cancer Gene Ther 6:313–321
Stanley R, Lauri A (eds) (2000) WHO classification of tumors. Pathology and genetics of tumors of the digestive system. IARC, Lyon, p 113
Mauri FA, Caffo O, Veronese S, Verderio P, Boracchi P, Bonzanini M, Rossi N, Perrone G, Dalla Palma P, Barbareschi M (1998) Tissue carcinoembryonic antigen and oestrogen receptor status in breast carcinoma: an immunohistochemical study of clinical outcome in a series of 252 patients with long-term follow-up. Br J Cancer 77:1661–1668
He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281(5382):1509–1512 (Sep 4)
Chen RH, Ding WV, McCormick F (2000) Wnt signaling to beta-catenin involves two interactive components. Glycogen synthase kinase-3beta inhibition and activation of protein kinase C. J Biol Chem 275(23):17894–17899 (Jun 9)
Serge J, Song-Yang Y, Kinji S (1993) Transcription of carcinoembryonic antigen in normal colon and colon carcinoma. Am J Pathol 143:250–257
Edlund M, Gaardsvoll H, Bock E, Obrink B (1993) Different isoforms and stock-specific variants of the cell adhesion molecule C-CAM (cell-CAM 105) in rat liver. Eur J Biochem 213:1109–1116
Ulla S, Björn Ö (2001) CEACAM1 isoforms with different cytoplasmic domains show different localization, organization and adhesive properties in polarized epithelial cells. J Cell Sci 115:1273–1284
Baum PA, Troll S, Hixson DC (1996) The long and the short isoform of cell-CAM 105 show variants-specific modifications in adult rat organs. Biochem Biophys Res Commun 227:775–781
Singer BB, Scheffran I, Öbrink B (2000) The tumor growth-inhibiting cell adhesion molecule CEACAM1 (C-CAM1) is differently expressed in proliferating and quiescent epithelial cells and regulates cell proliferation. Cancer Res 60:1236–1244
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Kang, WY., Chen, WT., Wu, MT. et al. The expression of CD66a and possible roles in colorectal adenoma and adenocarcinoma. Int J Colorectal Dis 22, 869–874 (2007). https://doi.org/10.1007/s00384-006-0247-x
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DOI: https://doi.org/10.1007/s00384-006-0247-x