Carcinoembryonic Antigen (CEA)

CEA is a large family of 36 different, but related, glycoproteins, which are part of the immunoglobulin superfamily. The human CEA gene family is clustered on chromosome 19q and comprises 29 genes. Seven of these 29 genes code for CEA glycoproteins. CEA molecules exhibit considerable heterogeneity due to variation in carbohydrate side chains.

CEA is present in the gastrointestinal tract during fetal life and occurs at low concentrations in adults. CEA was first reported to be quite specific for tumors of the GI tract, but further investigations demonstrated elevations in several other malignant and benign diseases. Elevated CEA levels are suggestive, but not diagnostic of cancer, since elevated levels also occur in a variety of benign conditions:

  • Most normal persons have detectable concentrations of circulating CEA. Approximately 85% of adults have CEA levels less than 2.5 ng/mL, while 95% have levels less than 5.0 ng/mL. CEA levels are slightly higher in men than women. The median level is 3.4 ng/mL in men and 2.5 ug/mL in women. Healthy persons seldom have levels above 10 ng/mL
  • CEA concentrations are twice as high in smokers; female smokers have a median CEA level of 4.9 ng/mL and male smokers have a median level of 6.2 ng/mL.
  • CEA levels are not elevated in maternal serum during pregnancy, since CEA does not cross the placenta.
  • The liver is the primary site for metabolism of CEA. Benign diseases that impair liver function reduce CEA clearance, resulting in increased serum levels. CEA levels are elevated in 70% of patients with chronic liver disease and 50% of patients with acute liver disease.
  • Elevated levels are also frequently seen in other gastrointestinal diseases including peptic ulcer, pancreatitis, diverticulitis, and inflammatory bowel disease. Benign diseases rarely produce CEA serum levels >10ng/mL.
  • CEA levels are slightly elevated in patients with chronic renal failure undergoing dialysis.

Serum CEA is ordered most often for patients with colorectal cancer. Numerous studies have demonstrated that:

  • Serum concentrations of CEA tend to be higher in patients with well-differentiated colon cancer compared with poorly differentiated cancer.
  • Patients with tumors in the left side of the colon generally have a higher incidence of increased CEA concentrations than those with tumors on the right side.
  • Bowel obstruction results in higher CEA concentrations in patients with colorectal cancer. Decompression alone reduces serum CEA levels.

Serum CEA is not sensitive enough to be used as a screening test for colorectal cancer. The goal of colorectal cancer screening should be to detect disease at either stage I (Duke’s A) or II (Duke’s B). Using a cutoff of 2.5 ng/mL, CEA is elevated in only 30% of patients with stage I and II cancer. CEA levels cannot distinguish locally invasive premalignant colonic polyps from benign polyps.

Duke’s staging system has been the gold standard for predicting outcome in patients with newly diagnosed colorectal cancer. Additional prognostic factors are particularly needed for patients with stage II (Duke’s B, node-negative) colorectal cancer because 40 to 50% of these patients have aggressive disease and might benefit from adjuvant chemotherapy. The majority of studies suggest that preoperative CEA levels can provide prognostic data in patients with stage II colorectal cancer. High levels are associated with more aggressive disease.

The circulatory half-life of CEA is ~7 days. After successful surgical resection of colorectal cancer, an increased CEA concentration should return to normal within 4 to 6 weeks. Failure of an increased preoperative level to decrease in to the normal range within 6 weeks of surgery frequently is associated with recurrent disease.

The use of serial CEA levels to follow patients who have no evidence of disease after primary therapy is more controversial. Serial CEA determinations are most useful in detecting liver metastasis. Sensitivity and specificity are approximately 90%. Hepatic resection for isolated liver metastases achieves long-term survival in 20 to 50% of patients and may be the only curative therapy for metastatic colorectal cancer. Because of this success, the American Society of Clinical Oncology (ASCO) recommends CEA monitoring only in those patients with stage II and III (Duke’s C) disease who are willing and able to undergo a hepatic resection for metastatic disease. For this subset, CEA monitoring is recommended every 2 to 3 months for at least 2 years after diagnosis.

CEA has a much lower sensitivity and specificity for detection of local recurrence after successful primary therapy. A compilation of data from several studies suggests that elevations in CEA correlate with relapse only 40% of the time. That means that 60% of the time, CEA levels were falsely elevated. However, CEA does appear to be superior to endoscopy, computerized tomograpy and ultrasound in diagnosing local recurrences. Monitoring with CEA can detect recurrent colorectal cancer with an average lead-time of 5 months (range, 4 to 10 months) before these other modalities. ASCO has not endorsed serial CEA monitoring for local recurrence.

Fluorouracil-based chemotherapy enhances outcome in some patients with advanced colorectal cancer. Because CEA is increased in >80% of patients with distant metastases, it is a potential marker for monitoring response to chemotherapy. ASCO recommends obtaining a baseline CEA value before treatment and serial monitoring every 2 to 3 months during treatment. Two values above the baseline are adequate to document progressive disease and discontinuation of therapy, even in the absence of corroborating radiological evidence.However, in spite of this recommendation, it is important to realize that chemotherapy can cause transient increases in CEA concentration due to hepatic toxicity in the absence of disease progression.

Reference range is 0 - 5 ng/mL. A difference of >20% between two CEA measurements is considered medically significant.

Specimen requirement is one red top tube of blood.

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