Carcinoembryonic antigen

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Carcinoembryonic antigen (CEA) describes a set of highly related glycoproteins involved in cell adhesion. CEA is normally produced in gastrointestinal tissue during fetal development, but the production stops before birth. Therefore, CEA is usually present only at very low levels in the blood of healthy adults. However, the serum levels are raised in some types of cancer, which means that it can be used as a tumor marker in clinical tests. Serum levels can also be elevated in heavy smokers.[2]

CEA are glycosyl phosphatidyl inositol (GPI) cell-surface-anchored glycoproteins 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.[3][4][5] Immunologically they are characterized as members of the CD66 cluster of differentiation. The proteins include CD66a, CD66b, CD66c, CD66d, CD66e, CD66f.

History

CEA was first identified in 1965 by Phil Gold and Samuel O. Freedman in human colon cancer tissue extracts.[6]

Diagnostic significance

The CEA blood test is not reliable for diagnosing cancer or as a screening test for early detection of cancer.[7] Most types of cancer do not result in a high CEA level.

Serum from individuals with colorectal carcinoma often has higher levels of CEA than healthy individuals (above approximately 2.5 µg/L).[8] CEA measurement is mainly used as a tumor marker to monitor colorectal carcinoma treatment, to identify recurrences after surgical resection, for staging or to localize cancer spread through measurement of biological fluids.[9] CEA levels may also be raised in gastric carcinoma, pancreatic carcinoma, lung carcinoma, breast carcinoma, and medullary thyroid carcinoma, as well as some non-neoplastic conditions like ulcerative colitis, pancreatitis, cirrhosis,[10] COPD, Crohn's disease, hypothyroidism [11] as well as in smokers. Elevated CEA levels should return to normal after successful surgical removal of the tumor. of what? for what?.

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 and, thus, varies directly with tumor stage. Left-sided tumors generally tend to have higher CEA levels than right-sided tumors. Tumors causing bowel 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.[12]

Regions of high CEA levels in the body can be detected with the monoclonal antibody arcitumomab.

Antibodies to CEA are also commonly used in immunohistochemistry to identify cells expressing the glycoprotein in tissue samples. In adults, CEA is primarily expressed in cells of tumors (some malignant, some benign) but they are particularly associated with the 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.[13]

Genetics

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.[14] 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

References

  1. ↑ 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. PMID 10854848. doi:10.1016/S0014-5793(00)01612-4.
  2. ↑ Duffy, Michael J. (2001-04-01). "Carcinoembryonic Antigen as a Marker for Colorectal Cancer: Is It Clinically Useful?". Clinical Chemistry. 47 (4): 624–630. ISSN 0009-9147. PMID 11274010.
  3. ↑ 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. PMC 2414264 Freely accessible. PMID 18375392. doi:10.1074/jbc.M800543200.
  4. ↑ Konstantopoulos K, Thomas SN (2009). "Cancer cells in transit: the vascular interactions of tumor cells". Annu Rev Biomed Eng. 11: 177–202. PMID 19413512. doi:10.1146/annurev-bioeng-061008-124949.
  5. ↑ 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. PMID 19581728. doi:10.3233/BIR-2009-0534.
  6. ↑ 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 Freely accessible. PMID 14270243. doi:10.1084/jem.121.3.439.
  7. ↑ Duffy, M. J.; Van Dalen, A.; Haglund, C.; Hansson, L.; Klapdor, R.; Lamerz, R.; Nilsson, O.; Sturgeon, C.; Topolcan, O. (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. PMID 12651195. doi:10.1016/S0959-8049(02)00811-0.
  8. ↑ Ballesta, AM; Molina, R; Filella, X; Jo, J; Giménez, N (1995). "Carcinoembryonic antigen in staging and follow-up of patients with solid tumors.". Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 16 (1): 32–41. PMID 7863220. doi:10.1159/000217926.
  9. ↑ Duffy, Michael J. (April 2001). "Carcinoembryonic Antigen as a Marker for Colorectal Cancer: Is It Clinically Useful?". Clinical Chemistry. 47 (4): 624–630.
  10. ↑ 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 (1): 99–103. PMID 9463746. doi:10.1177/000456329803500113.
  11. ↑ De Mais, Daniel. ASCP Quick Compendium of Clinical Pathology, 2nd Ed. ASCP Press 2009.
  12. ↑ Duffy, Michael J. (2001-04-01). "Carcinoembryonic Antigen as a Marker for Colorectal Cancer: Is It Clinically Useful?". Clinical Chemistry. 47 (4): 624–630. ISSN 0009-9147. PMID 11274010.
  13. ↑ 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.
  14. ↑ 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. PMID 10202129. doi:10.1006/scbi.1998.0119.
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