CEA

Synonyms: Carcinoembryonic antigen, CD66e, CEACAM5

by Jan Klos

Background

Carcinoembryonic antigen (CEA, CD66e) is a 180-200 kDa glycoprotein, member of CEA gene family located on chromosome 19q13.2. CEA and the other members of the CEA family belong to the immunoglobulin superfamily. The human CEA family comprises 29 genes, divided in three subgroups of which 18 are expressed; 7 belong to the CEA subgroup, 11 to the pregnancy specific glycoprotein subgroup and the third subgroup containing six members.

The functions of the CEA family are unknown, but they can act as homophilic and heterophilic cell adhesion molecules. Further they have roles in signal transduction, cooperation with proto-oncogenes in cellular transformation and inhibition of proliferation of epithelial tumors. CEA is a oncofetal antigen that normally is present during fetal life, occurs at low concentrations in adults, and circulate in high concentrations in patients with certain malignancies, particularly epithelial tumors.

Staining in normal cells/tissues: In normal adult tissue, CEA is expressed in the apical border and to a lesser extent in the cytoplasm, of the columnar cells of gastro-intestinal tract (colon, small intestine, stomach – surface epithelium, mucous neck cells and weakly expressed in pyloric mucous cells), pancreatic ducts, secretory epithelia of sweat glands, squamous epithelial cells of the tongue, esophagus, uterine cervix, and urothelium.

Staining in tumors: The expression of CEA is upregulated in many types of carcinomas.

  • CEA is expressed in epithelial cell membranes and in the cytoplasm of almost all cases of colorectal adenocarcinoma as well as a high proportion of adenocarcinomas of the salivary glands, esophagus, stomach, biliary tract, pancreas, small intestine, lung, uterine cervix and ovary (mucinous type).
  • CEA is seen less frequently in breast carcinoma, ovarian Brenner tumor and endometrioid carcinoma.
  • Among neuroendocrine tumors, CEA is found in the large majority of medullary thyroid carcinoma, less often and more weakly expressed in carcinoid tumor, neuroendocrine carcinoma and rarely in small cell carcinoma.
  • In urothelial malignancies, CEA is particularly seen in high grade lesions.
  • Among germ cell tumors, CEA is seen in most cases of embryonal carcinoma but rarely in the other types.
  • CEA is detected in squamous cell carcinoma of esophagus and uterine cervix.
  • Among non-epithelial tumors, CEA may be detected in secretory meningioma (but not in other meningioma types), synovial sarcoma and epithelioid sarcoma.
  • Malignant mesothelioma is always negative (provided that the Ab does not cross react with other CEA-like epitopes).
  • The following carcinomas are rarely CEA positive: ovarian serous and clear cell carcinoma, renal cell carcinoma, adrenal cortical carcinoma, prostate adenocarcinoma, hepatocellular carcinoma (except for the rare fibrolamellar variant) and follicular and papillary thyroid carcinoma.
  • Polyclonal CEA reacts with biliary glycoprotein in primary bile canaliculi in hepatocellular carcinoma.

Staining pattern: cytoplasmic

Control tissue: Appendix in which the enterocytes should be distinctively stained, no reaction should be seen in other cells or structures.

Application: CEA monoclonal antibodies are mostly used in panels in differential diagnosis of

  • malignant mesothelioma (negative) and peripheral pulmonary adenocarcinoma (positive) or a number of metastatic adenocarcinomas in pleura (majority is positive),
  • hepatocellular carcinoma from cholangiocarcinoma and a number of metastatic adenocarcinomas in liver,
  • endocervical (positive) and endometrioid  adenocarcinoma (circa 10% positive) except mucinous type,
  • adenocarcinomas of digestive tract (mostly positive),
  • skin adnexal tumors, to distinguish sweat gland tumors (positive) from hair follicle derived and sebaceous tumors (negative).

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