Carcinoembryonic antigen (CEA) test

Carcinoembryonic Antigen (CEA) Overview

Carcinoembryonic Antigen (CEA) is a glycoprotein involved in cell adhesion. It is classified as an oncofetal antigen because it is produced normally at high levels during fetal development, primarily by the gastrointestinal tract tissues. After birth, CEA production is significantly suppressed, and levels in the blood of healthy adults are usually very low.

Elevated levels of CEA can be found in the blood of people with certain types of cancer, particularly colorectal cancer, as well as some other malignancies and benign conditions. Therefore, CEA testing is primarily used as a tumor marker for monitoring cancer treatment and detecting recurrence, rather than for screening or initial diagnosis.

CEA Biology and Structure

CEA belongs to the CEA family of cell adhesion molecules (CEACAMs). It is a large glycoprotein with a molecular weight ranging from 175 to 200 kDa, characterized by a high carbohydrate content (up to 60%), which contributes to its heterogeneity. During electrophoresis, it typically migrates in the beta (β)-globulin region.

While CEA levels are very low in most healthy adults, small amounts can be found in some normal tissues like the colon, liver, and pancreas. Its production can increase significantly in various cancers, particularly adenocarcinomas originating from the gastrointestinal tract.

Clinical Indications for CEA Testing

The primary uses of the CEA test in oncology include:

1. Monitoring Colorectal Cancer:
   • Assessing prognosis after diagnosis (higher preoperative levels often correlate with more advanced stage and poorer prognosis).
   • Monitoring response to treatment (surgery, chemotherapy, radiation). A significant drop after surgery suggests complete resection. Failure to normalize or subsequent rise suggests residual disease or ineffective therapy.
   • Surveillance for recurrence after curative treatment. Rising CEA levels during follow-up are often the first sign of recurrence (local or metastatic), prompting further investigation with imaging.
2. Monitoring Other Cancers: CEA can also be elevated and used for monitoring (though often less reliably than for colorectal cancer) in other malignancies, including:
   • Medullary Thyroid Carcinoma (MTC): CEA is often used alongside calcitonin for monitoring.
   • Lung Cancer (especially adenocarcinoma)
   • Breast Cancer
   • Pancreatic Cancer
   • Gastric Cancer
   • Ovarian Cancer
   • Other gastrointestinal or genitourinary cancers.
3. Diagnosis Support (Limited Role): While not used for screening, a very high CEA level in a patient with symptoms suggestive of cancer might increase suspicion for certain types, particularly metastatic colorectal cancer. Its use in diagnosing C-cell thyroid carcinoma (MTC) alongside calcitonin is established.

CEA is generally not recommended for cancer screening in the general population due to its low sensitivity and specificity.

Interpretation of CEA Levels

Interpretation must consider the clinical context, patient history (especially smoking status), and reference ranges of the specific laboratory.

• Normal Range: Varies slightly by lab, but generally:
  • Non-smokers: Typically < 2.5 - 3.0 ng/mL (or µg/L). Some labs use up to 5 ng/mL.
  • Smokers: Can have higher baseline levels, often up to 5.0 - 10.0 ng/mL, due to smoking-related inflammation or cellular changes.
  • Note: The original text mentioned a normal range up to 3 kg/ml which is incorrect; units are typically ng/mL or µg/L. The value of 5 ng/mL is a common upper limit for non-smokers.
• Elevated Levels in Cancer:
  • Levels often correlate with tumor burden and stage, particularly in colorectal cancer. Very high levels usually indicate metastatic disease.
  • Sensitivity varies by cancer type and stage. CEA may be elevated in 50-90% of patients with colorectal, gastric, or pancreatic cancer (higher percentages in advanced stages), but less frequently in breast (30-50%) or lung cancer.
  • In untreated or progressing malignancy, CEA levels typically rise over time.
  • Successful treatment should lead to a decrease in elevated CEA levels. The rate of decline after surgery can have prognostic value.
  • A persistent elevation or rise after treatment strongly suggests residual disease or recurrence.
• Elevated Levels in Benign Conditions: Mild to moderate elevations (usually < 10 ng/mL, rarely slightly higher) can be seen in 20-50% of patients with various non-malignant inflammatory or benign proliferative conditions, including:
  • Liver disease (cirrhosis, chronic hepatitis)
  • Inflammatory Bowel Disease (ulcerative colitis, Crohn's disease)
  • Pancreatitis
  • Lung disease (pneumonia, bronchitis, tuberculosis, emphysema, COPD)
  • Peptic ulcer disease
  • Gallbladder disease
  • Diverticulitis
  • Benign breast disease
  • Renal failure
  • Autoimmune diseases
  • Importantly, Smoking is a common cause of mildly elevated CEA.
  In these benign conditions, CEA levels typically remain stable or decrease with clinical improvement, unlike the progressive rise often seen with malignancy.

Factors Affecting CEA Levels

• Smoking: Significantly elevates baseline CEA levels.
• Age: May slightly increase with age.
• Benign Inflammatory/Proliferative Conditions: As listed above.
• Cancer Type, Stage, and Burden: Primary determinant of significant elevations.
• Treatment: Surgery, chemotherapy, radiation can lower levels if effective.
• Liver Function: CEA is partly metabolized by the liver; severe liver dysfunction could potentially affect levels.

Limitations and Considerations

• Low Specificity: Elevated levels occur in many benign conditions and in smokers.
• Low Sensitivity: Often normal in early-stage cancers and not elevated in all patients even with advanced disease.
• Screening Inappropriateness: Not suitable for general cancer screening.
• Monitoring Value: Most useful for monitoring trends over time in diagnosed patients, especially for colorectal cancer recurrence. A consistent rise is more significant than a single elevated value.
• Smoking Status: Essential information for interpreting CEA levels.

The CEA Blood Test Procedure

• Sample Type: Blood serum or plasma.
• Preparation: No specific patient preparation like fasting is typically required. Inform the provider about smoking status.
• Collection: Standard venipuncture (blood draw from a vein).
• Analysis: Measured in a clinical laboratory using immunoassays.

References

1. National Cancer Institute (NCI). (n.d.). Tumor Markers. NCI Dictionary of Cancer Terms. Retrieved from https://www.cancer.gov/publications/dictionaries/cancer-terms/def/tumor-marker
2. American Cancer Society (ACS). (2023). Tumor Markers. Retrieved from https://www.cancer.org/cancer/diagnosis-staging/tests/tumor-markers.html
3. Locker, G. Y., Hamilton, S., Harris, J., Jessup, J. M., Kemeny, N., Macdonald, J. S., ... & Hayes, D. F. (2006). ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. *Journal of Clinical Oncology*, 24(33), 5313–5327. https://doi.org/10.1200/JCO.2006.08.2644
4. Duffy, M. J., Lamerz, R., Haglund, C., Nicolini, A., Topolcan, O., Sturgeon, C., & Hayes, D. F. (2014). Tumor markers in colorectal cancer, gastric cancer and gastrointestinal stromal cancers: a European Group on Tumor Markers (EGTM) status report. *International Journal of Cancer*, 134(12), 2911–2922. https://doi.org/10.1002/ijc.28390
5. Mayo Clinic Laboratories. (n.d.). Test ID: CEA - Carcinoembryonic Antigen (CEA), Serum. Test Catalog. Retrieved from https://www.mayocliniclabs.com/test-catalog/Overview/8324 (Example lab reference)
6. Lab Tests Online. (n.d.). CEA. Retrieved from https://labtestsonline.org/tests/cea