Carcinoembryonic antigen
Carcinoembryonic antigen (CEA) is a glycoprotein involved in cell adhesion. It is normally produced during fetal development, but the production of CEA stops before birth. Therefore, it is not usually present in the blood of healthy adults, although levels are raised in heavy smokers. CEA is a glycosyl phosphatidyl inositol (GPI)-cell surface anchored glycoprotein whose specialized sialofucosylated glycoforms serve as functional colon carcinoma L-selectin and E-selectin ligands, which may be critical to the metastatic dissemination of colon carcinoma cells.[2][3][4]
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History[edit]
CEA was first identified in 1965 by Phil Gold and Samuel O. Freedman in human colon cancer tissue extracts.[5]
Diagnostic significance[edit]
It was found that serum from individuals with colorectal carcinoma,[6] gastric carcinoma, pancreatic carcinoma, lung carcinoma and breast carcinoma, as well as individuals with medullary thyroid carcinoma, had higher levels of CEA than healthy individuals (above 2.5 ng/ml).
CEA elevation is known to be affected by multiple factors. It varies inversely with tumor grade (well-differentiated tumors secrete more CEA). CEA is elevated more in tumors with lymph node and distant metastasis than in organ-confined tumors (varies directly with tumor stage). Left-sided tumors tend to have higher CEA levels than right-sided tumors. Tumors causing obstruction produce higher CEA levels. Aneuploid tumors produce more CEA than diploid tumors. Liver dysfunction increases CEA levels as the liver is the primary site of CEA metabolism.
CEA levels are higher for smokers than for nonsmokers. Other nonneoplastic causes of elevated CEA include inflammatory bowel disease, peptic ulcer disease, pancreatitis, biliary disease, liver dysfunction (as stated above) and hypothyroidism. [7]
Regions of high CEA levels in the body can be detected with the monoclonal antibody arcitumomab.[clarification needed]
CEA measurement is mainly used[citation needed] as a tumor marker to identify recurrences after surgical resection, or localize cancer spread through dosage of biological fluids. The CEA blood test is not reliable for diagnosing cancer or as a screening test for early detection of cancer.[8] Most types of cancer do not produce a high CEA. Elevated CEA levels should return to normal after successful surgical resection, or within 6 weeks of starting treatment if cancer treatment is successful.[citation needed]
CEA levels may also be raised in some non-neoplastic conditions like ulcerative colitis, pancreatitis, cirrhosis,[9] COPD, Crohn's disease as well as in smokers.[citation needed]
The antigen CEA has been licensed by the Dendreon Corp for development as an Autologous Cellular Immunotherapy. Product candidates targeted at CEA are in preclinical development for the treatment of breast, lung, and colon cancer.
Antibodies to CEA are also commonly used in immunohistochemistry to identify cells expressing the glycoprotein in tissue samples. In adults, CEA is expressed only in cancer cells, especially adenocarcinomas, such as those arising in the colon, lung, breast, stomach, or pancreas. It can therefore be used to distinguish between these and other similar cancers. For example, it can help to distinguish between adenocarcinoma of the lung and mesothelioma, a different type of lung cancer which is not normally CEA positive. Because even monoclonal antibodies to CEA tend to have some degree of cross-reactivity, occasionally giving false positive results, it is commonly employed in combination with other immunohistochemistry tests, such as those for BerEp4, WT1, and calretinin.[10]
Genetics[edit]
CEA and related genes make up the CEA family belonging to the immunoglobulin superfamily. In humans, the carcinoembryonic antigen family consists of 29 genes, 18 of which are normally expressed.[11]
The following is a list of human genes which encode carcinoembryonic antigen-related cell adhesion proteins:
CEACAM1, CEACAM3, CEACAM4, CEACAM5, CEACAM6, CEACAM7, CEACAM8, CEACAM16, CEACAM18, CEACAM19, CEACAM20, CEACAM21
See also[edit]
References[edit]
- ^ Boehm, M. K.; Perkins, S. J. (2000). "Structural models for carcinoembryonic antigen and its complex with the single-chain Fv antibody molecule MFE23". FEBS Letters 475 (1): 11–16. doi:10.1016/S0014-5793(00)01612-4. PMID 10854848.
- ^ Thomas SN, Zhu F, Schnaar RL, Alves CS, Konstantopoulos K (Jun 2008). "Carcinoembryonic antigen and CD44 variant isoforms cooperate to mediate colon carcinoma cell adhesion to E- and L-selectin in shear flow". J Biol Chem 283 (23): 15647–55. doi:10.1074/jbc.M800543200. PMC 2414264. PMID 18375392.
- ^ Konstantopoulos K, Thomas SN (2009). "Cancer cells in transit: the vascular interactions of tumor cells". Annu Rev Biomed Eng 11: 177–202. doi:10.1146/annurev-bioeng-061008-124949. PMID 19413512.
- ^ Thomas SN, Tong Z, Stebe KJ, Konstantopoulos K (2009). "Identification, characterization and utilization of tumor cell selectin ligands in the design of colon cancer diagnostics". Biorheology 46 (3): 207–25. doi:10.3233/BIR-2009-0534. PMID 19581728.
- ^ Gold P, Freedman SO (March 1965). "DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES.". The Journal of experimental medicine 121: 439–62. PMC 2137957. PMID 14270243.
- ^ "Cancer Diagnosis - Information About Cancer - Stanford Cancer Center". Retrieved 2008-10-15.
- ^ De Mais, Daniel. ASCP Quick Compendium of Clinical Pathology, 2nd Ed. ASCP Press 2009.
- ^ Duffy, M. J.; Van Dalen, A.; Haglund, C.; Hansson, L.; Klapdor, R.; Lamerz, R.; Nilsson, O.; Sturgeon, C. et al. (2003). "Clinical utility of biochemical markers in colorectal cancer: European Group on Tumour Markers (EGTM) guidelines". European journal of cancer (Oxford, England : 1990) 39 (6): 718–727. doi:10.1016/S0959-8049(02)00811-0. PMID 12651195.
- ^ Maestranzi, S.; Przemioslo, R.; Mitchell, H.; Sherwood, RA. (Jan 1998). "The effect of benign and malignant liver disease on the tumour markers CA19-9 and CEA.". Ann Clin Biochem. 35 ( Pt 1): 99–103. PMID 9463746.
- ^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2 ed.). Greenwich Medical Media, Ltd. pp. 51–52. ISBN 1-84110-100-1.
- ^ Hammarström S (April 1999). "The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues*1". Seminars in Cancer Biology 9 (2): 67–81. doi:10.1006/scbi.1998.0119. PMID 10202129.
External links[edit]
- Carcinoembryonic Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
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