Carcinoembryonic antigen (CEA) is a glycoprotein, which is present in normal mucosal cells but increased amounts are associated with adenocarcinoma, especially colorectal cancer. CEA therefore has a role as a tumour marker. Levels exceeding 10 μg/L are rarely due to benign disease.¹

• Less than 25% of patients with disease confined to the colon have an elevated CEA level. Sensitivity increases with advancing tumour stage. However, poorly differentiated tumours are less likely to produce CEA.¹
• CEA values are increased in approximately 50% of patients with lymph node disease. Values are elevated in 75% of patients with distant metastasis.¹

CEA levels are useful in assessing prognosis (with other factors), detecting recurrence (especially for disease that cannot be evaluated by other means) and monitoring treatment in patients with colorectal cancer. CEA is particularly recommended for postoperative follow-up of patients with stage II and III colorectal cancer if further surgery or chemotherapy is an option.²

Conditions which may have elevated CEA³

• Colorectal cancer; tumours on the right side of the colon tend to produce higher CEA levels than tumours on the left side.
• Breast cancer.⁴
• Lung cancer.⁵
• Gastric cancer, oesophageal cancer, pancreatic cancer.
• Mesothelioma.
• Skeletal metastases.
• Non-malignant liver disease, including cirrhosis, chronic active hepatitis.⁶
• Chronic kidney disease.
• Pancreatic disease.⁷
• Inflammatory bowel disease, diverticulitis, irritable bowel syndrome.
• Respiratory diseases, e.g. pleural inflammation, pneumonia.
• Smoking.
• Ageing.⁸
• Atherosclerosis.⁸

Normal range

Studies of patients with colorectal tumours suggest that the CEA level deemed to be normal is 2.5 μg/L or less.³ This level can double in smokers.¹

Indications for CEA measurement

Colorectal cancer

• Diagnosis:
  • A CEA level should be ordered only after malignancy has been confirmed.
  • The CEA test has a specificity of between 30-80% and it is not recommended by the National Institute for Health and Clinical Excellence (NICE) for the diagnosis of early colorectal cancer.⁹
  • NICE does not recommend delaying referral for the results of any tests if there is sufficient clinical concern about the diagnosis.⁹
• Prognosis:
  • The CEA test is of much more use in determining prognosis than it is as an early diagnostic test for colon cancer.
  • CEA levels tend to be higher in advanced disease. One study found that using a cut-off point of 5 μg/L the proportions of patients with increased values were 3%, 25%, 45%, and 65% for patients with Dukes' A, B, C, and D disease respectively.³
• Staging:
  • CEA in combination with other tumour markers (e.g. mucin tumour markers CA19-9, CA242) can be used in preoperative staging and thereby assist in the planning of the type of surgery required and future management options.¹⁰
• Monitoring treatment:¹
  • The major role for CEA levels is in following patients for relapse after intended curative treatment of colorectal cancer.
  • CEA levels typically return to normal within four to six weeks after successful surgical resection. The CEA level can also be used to assess the response to chemotherapy.
  • When patients with a normal preoperative CEA level have cancer recurrence, CEA elevation is a sign in nearly one half of them.
  • Clinical trials have shown a 9% improvement in survival after five years in patients who underwent CEA monitoring as part of post-treatment management. However, normal levels do not necessarily indicate that recurrence has not occurred.¹¹

Breast cancer

Similar considerations apply to the diagnosis of breast cancer. The sensitivity of CEA is too low for it to be used as a primary diagnostic test.¹²

In conjunction with other tumour markers (CA27.29, tissue polypeptide antigen and especially CA 15-3), it may however be helpful in disease surveillance,¹³ in identifying patients with skeletal metastases⁴ and in response to chemotherapy.¹⁴ One study suggested that it may be helpful in determining prognosis.¹⁵

Document references

1. Perkins GL, Slater ED, Sanders GK, et al; Serum tumor markers. Am Fam Physician. 2003 Sep 15;68(6):1075-82. [abstract]
2. Sturgeon CM, Lai LC, Duffy MJ; Serum tumour markers: how to order and interpret them. BMJ. 2009 Sep 22;339:b3527. doi: 10.1136/bmj.b3527.
3. Duffy MJ; Carcinoembryonic antigen as a marker for colorectal cancer: is it clinically useful? Clin Chem. 2001 Apr;47(4):624-30. [abstract]
4. Duffy MJ; Serum tumor markers in breast cancer: are they of clinical value? Clin Chem. 2006 Mar;52(3):345-51. Epub 2006 Jan 12. [abstract]
5. Molina R, Auge JM, Escudero JM, et al; Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as Tumor Markers in Patients with Lung Cancer: Comparison with CYFRA 21-1, CEA, SCC and NSE. Tumour Biol. 2008 Dec 8;29(6):371-380. [abstract]
6. Tsukushi S, Katagiri H, Kataoka T, et al; Serum tumor markers in skeletal metastasis. Jpn J Clin Oncol. 2006 Jul;36(7):439-44. Epub 2006 Jun 30. [abstract]
7. Dragovich T et al; Colon Adenocarcinoma, Medscape, May 2011
8. Ishizaka N, Ishizaka Y, Toda E, et al; Are serum carcinoembryonic antigen levels associated with carotid atherosclerosis in Japanese men? Arterioscler Thromb Vasc Biol. 2008 Jan;28(1):160-5. Epub 2007 Oct 19. [abstract]
9. Service guidance for the NHS in England and Wales Improving Outcomes for Colorectal Cancer (update), NICE (2004)
10. Levy M, Visokai V, Lipska L, et al; Tumor markers in staging and prognosis of colorectal carcinoma. Neoplasma. 2008;55(2):138-42. [abstract]
11. Hara M, Kanemitsu Y, Hirai T, et al; Negative serum carcinoembryonic antigen has insufficient accuracy for excluding recurrence from patients with Dukes C colorectal cancer: analysis with likelihood ratio and posttest probability in a follow-up study. Dis Colon Rectum. 2008 Nov;51(11):1675-80. [abstract]
12. Arslan N, Serdar M, Deveci S, et al; Use of CA15-3, CEA and prolactin for the primary diagnosis of breast cancer and correlation with the prognostic factors at the time of initial diagnosis. Ann Nucl Med. 2000 Oct;14(5):395-9. [abstract]
13. Brooks M; Breast cancer screening and biomarkers. Methods Mol Biol. 2009;472:307-21. [abstract]
14. Yonemori K, Katsumata N, Noda A, et al; Development and verification of a prediction model using serum tumor markers to predict the response to chemotherapy of patients with metastatic or recurrent breast cancer. J Cancer Res Clin Oncol. 2008 Nov;134(11):1199-206. Epub 2008 Jun 5. [abstract]
15. Uehara M, Kinoshita T, Hojo T, et al; Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer. Int J Clin Oncol. 2008 Oct;13(5):447-51. Epub 2008 Oct 23. [abstract]

Acknowledgements