Stains & CD markers
CEA / CD66e


Last author update: 6 July 2022
Last staff update: 6 July 2022

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PubMed Search: CEA

Related topics: General, CD66b, CD66c, CD66d, CD66f

Valeriya Skorobogatko, B.A.
Brandon Umphress, M.D.
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Cite this page: Skorobogatko V, Umphress B. CEA / CD66e. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainscea.html. Accessed January 30th, 2023.
Definition / general
  • Glycosyl phosphatidyl inositol (GPI) cell surface anchored glycoproteins that function as a ligand for various selectins
  • Immunohistochemical antibodies to carcinoembryonic antigen (CEA) are either polyclonal (pCEA) or monoclonal (mCEA)
Essential features
  • Usually considered an epithelial marker with expression in various adenocarcinomas
  • Can highlight ductal differentiation (i.e., poroma, porocarcinoma)
  • In addition to immunostaining, CEA is a nonspecific serum biomarker that can be elevated in various malignancies (e.g., colorectal cancer)
Terminology
  • CEA, carcinoembryonic antigen and CEACAM5
Pathophysiology
  • Normally detected in glycocalyx of fetal epithelial cells
  • Acts as a paracrine factor by activating fibroblasts through STAT3 and AKT1-mTORC1 signaling pathways and promoting their transformation into cancer associated fibroblasts (Int J Cancer 2018;143:1963)
  • Involved in mucosal colonization of bacteria: lipid A, a component of gram negative bacteria, may prevent the release of CEA from mucosal surfaces, facilitating bacterial colonization (Cell Mol Biol Lett 2015;20:374)
  • May play a role in the metastasis of cancer cells by protecting metastatic cells from death, promoting expression of adhesion molecules and survival of malignant cells; promotes angiogenesis (Recent Pat Biotechnol 2018;12:269)
Clinical features
  • Serum CEA is associated with colorectal carcinoma; preoperative levels can be associated with advanced or metastatic disease and poorer prognosis
  • Postoperatively, failure of CEA to return to normal has been found to be an indicator of residual or recurrent disease (Ann Coloproctol 2019;35:294)
  • Postoperative CEA levels can be useful for detecting early recurrence of lung adenocarcinoma (Korean J Thorac Cardiovasc Surg 2015;48:335)
  • Serum CEA is elevated in allergic bronchopulmonary aspergillosis (ABPA) (Sci Rep 2021;11:4025)
    • Increased CEA levels correlate with eosinophil levels indicating eosinophils may function to secrete CEA
  • Has been reported to be elevated in patients with COVID-19 pneumonia (J Cancer Res Clin Oncol 2020;146:3385)
  • Pure small cell lung cancer (SCLC) versus small cell lung cancer combined with other pathology (CSCLC): preoperative serum CEA > 6 ng/mL found more frequently in CSCLC than pure SCLC (Adv Clin Exp Med 2017;26:1091)
Interpretation
  • Variable cytoplasmic or membrane enhancement (focal / diffuse, weak / strong)
  • Varying intensities of circumferential staining in ductal differentiation of the skin
Uses by pathologists
  • Pulmonary adenocarcinoma: monoclonal CEA can demonstrate increased specificity for lung adenocarcinoma when compared with mesothelioma (Histopathology 2006;48:223)
    • CEA can help to distinguish metastatic lung adenocarcinoma (CEA+ in 53.8%, diffuse cytoplasmic staining with membrane enhancement) from mesothelioma in pleural effusions (Iran J Pathol 2019;14:122)
    • It is noted, however, that a panel of markers is recommended to more reliably differentiate between these 2 tumors
  • Distinguishes between hidradenomas (CEA+) and cutaneous clear cell renal cell carcinoma (CEA-) (J Cutan Pathol 2017;44:612)
  • Hepatocellular carcinoma: canalicular pattern for polyclonal CEA is 50 - 90% sensitive for hepatocellular carcinoma, > 95% specific (Mod Pathol 2002;15:1279)
  • Microvillous inclusion disease of small intestine: pCEA bright apical cytoplasmic blush / staining on surface enterocytes (Ultrastruct Pathol 2010;34:327)
  • Cysts (various): CEA levels > 5 ng/dL in ascites fluid are associated with malignancy (J Clin Pathol 2001;54:831)
Prognostic factors
  • Breast carcinoma: 88.3% specific and 46.2% sensitive for diagnosis of metastatic disease (Cancer Treat Res Commun 2021;28:10040)
  • Cholangiocarcinoma: elevated CEA levels associated with decreased survival (Sci Rep 2017;7:16975)
  • Colorectal carcinoma: monitor serum levels to detect recurrence (Int J Biol Markers 2019;34:60)
  • Elevated levels are preoperatively associated with a worse 3 year overall survival in invasive urothelial carcinoma (Urol Oncol 2014;32:648)
  • Esophageal adenocarcinoma: elevated pretreatment CEA levels are associated with early treatment failure and decreased overall survival (Am J Clin Oncol 2019;42:345)
  • Extramammary Paget disease (EMPD): CEA levels predict metastasis and treatment response (Br J Dermatol 2019;181:535)
  • Gallbladder carcinoma: CEA > 5 ng/mL can predict metastatic disease in anicteric patients with 80% specificity and 52% sensitivity (BMC Cancer 2020;20:826)
  • Gastric carcinoma: elevated levels aid in diagnosis and are associated with lymph node metastasis (BMC Gastroenterol 2020;20:100)
  • Higher values are associated with unresectable esophageal cancer; is an accurate biomarker of occult advanced disease (World J Surg 2015;39:424)
  • Intraductal papillary mucinous neoplasm of pancreas: high CEA level in pancreatic juice is an independent predictor of malignant transformation within 5 years (hazard ratio 17, p = 0.02) (J Gastroenterol 2019;54:1029)
  • Lung adenocarcinoma: elevated levels in nonlepidic histologic subtype associated with decreased 5 year survival (Asian Pac J Cancer Prev 2015;16:3857)
  • Medullary thyroid cancer: CEA > 271 ng/mL associated with advanced tumor size, staging, metastasis to central compartment and decreased chance of biochemical cure; CEA > 500 ng/mL associated with significant mortality (J Otolaryngol Head Neck Surg 2018;47:55)
  • Pancreatic adenocarcinoma: monoclonal CEA is 92% sensitive for metastases versus 0% for bile duct adenoma (Am J Surg Pathol 2005;29:381)
    • Elevated in 30 - 60% of pancreatic cancer patients and high CEA, > 5 ng/mL, is associated with decreased overall survival (Pancreatology 2016;16:859)
Microscopic (histologic) images

Contributed by Brandon Umphress, M.D. and Andrey Bychkov, M.D., Ph.D.

Porocarcinoma, ductal differentiation

Porocarcinoma with invasion into the dermis

Acrosyringeal unit


CEA expression in a poorly differentiated carcinoma

C cells in relation to thyroid follicle

Clustered C cells

Positive staining - normal
  • Eccrine sweat glands
  • Granulocytes and epithelial cells (apical surfaces)
  • Biliary tract including gallbladder, colon (fetal), hepatocytes, prostatic secretory cells (25%) and small intestinal crypts
  • Small intestinal goblet cell mucin (not intracytoplasmic), thyroid cell nests and C cells
Positive staining - not malignant
Positive staining - malignant
Negative staining - disease
Sample pathology report
  • Leg, right anterior, excisional biopsy:
    • Porocarcinoma (see comment)
    • Comment: Histologic sections demonstrate an infiltrating tumor extending into the deep dermis, characterized by significant pleomorphism with areas of ductal formation in a background of hyalinized to desmoplastic stroma. CEA and EMA highlight foci of ductal differentiation, while BerEP4 and MelanA are negative within the lesional cells of interest. The morphologic and immunophenotypic findings are most consistent with a porocarcinoma.
Board review style question #1
Serum CEA levels could be useful for monitoring recurrence of which disease state?

  1. Basal cell carcinoma
  2. Colorectal carcinoma
  3. Leiomyosarcoma
  4. Melanoma
Board review style answer #1
B. Colorectal carcinoma. Serum CEA levels can be elevated in colorectal carcinoma and can be useful in detecting possible recurrence.

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Reference: CEA / CD66e
Board review style question #2

Which of the following malignancies would most likely demonstrate CEA expression?

  1. Melanoma
  2. Mesothelioma
  3. Papillary thyroid carcinoma
  4. Porocarcinoma
Board review style answer #2
D. Porocarcinoma. CEA immunostaining can highlight the presence of ductal formation, aiding in the diagnosis of porocarcinoma. Melanoma, mesothelioma and papillary thyroid carcinoma typically do not express CEA.

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Reference: CEA / CD66e
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