Tumor Marker:- Part 11 – Carcinoembryonic Antigen (CEA)

Sample

1. This test is done on the serum of the patient.
2. The serum is stable for 24 hours at 2 to 8 °C.
3. For a long time, freeze the serum at -20 °C.
4. Some methods may use plasma.
   1. For plasma use EDTA 2mg/mL.
5. No special preparation is needed.
6. This test can be done on peritoneal fluid and CSF if it is raised to indicate tumor metastasis.

Precautions

1. Smokers have a higher CEA level.
2. Keep in mind about the benign conditions like colitis, diverticulitis, and cholecystitis give raised CEA level.
3. Also, liver diseases give raised the CEA level.

Purpose of the test (Indications)

1. CEA is a tumor marker for:
   1. Colorectal carcinoma.
   2. Gastrointestinal carcinoma.
   3. Lungs malignancies.
   4. Breast cancers.
2. This is a tumor marker and used to find the extent of disease in patients particularly gastrointestinal cancers.
3. This may be used in breast cancers.
4. This test is used to monitor the disease and treatment.

Pathophysiology

1. CEA was discovered in 1965 by the Gold and Freeman.
   1. This was found in the serum of a patient with colorectal carcinoma.
      1. Thus this CEA antigen was considered the indicator of colorectal cancers.
      2. Later on found in the other various tumors like breast, stomach, pancreas and hepatobiliary tumors, and sarcomas.
      3. This was also found in benign conditions like ulcerative colitis, cirrhosis, and diverticulitis.
      4. Chronic smokers also have raised the level of CEA.
   2. The tissue which is found in embryonic tissue is called carcinoembryonic antigen (CEA).
      1. CEA is normally found in the fetal gut tissue.
      2. By the time of the birth detectable level of CEA disappears.
   3. There are about 10 genes located on the chromosomes 19 encode the CEA protein.
   4. This is a glycoprotein with a molecular weight of 150 to 300 k

2. CEA is a tumor-associated, oncofetal antigen seen in embryonic and fetal tissue.
3. CEA is a glycoprotein which normally occurs in fetal gut tissue.
4. CEA is increased by 30% of colorectal, lung, liver, pancreas, breast, head and neck, urinary bladder, cervix, prostate, and medullary thyroid carcinoma.
   1. This is more specific for colorectal carcinoma.

5. In a patient with colorectal carcinoma, its level correlates with the tumor stage, tumor grade, and tumor site.
   1. Well-differentiated tumors produce more CEA than poorly differentiated tumors.
6. CEA is less commonly increased in lymphoma, leukemia, and malignant melanoma.
7. CEA also has been seen in an HIV-positive patient with P.C.carinii, a heavy smoker, and inflammatory bowel disease.
   1. This is metabolized in the liver so in liver disease is increased.
   2. Its median value is higher for smokers than non-smokers.
8. It is useful for monitoring GIT cancer especially colorectal carcinoma.
9. CEA is increased 60 to 90% of metastasis of lung cancer.
10. If the CEA level increase after surgery than the baseline is indicative of recurrence of the tumor.
    1. Patient with high preoperative concentration has a poor prognosis than those who have low values.

Drawbacks of CEA

1. CEA can be detected in benign and malignant conditions.
2. CEA is not raised in all colorectal cancers. Therefore not a reliable screening test.
   1. Its use is limited to know the prognosis and monitoring the tumor response to antineoplastic therapy in patients with cancer.
   2. CEA is helpful in patients with breast and gastrointestinal malignancies.

Normal

Source 1

Nonsmoker

• 99% = <5 ng/mL
• 1%   = 5.1 to 10 ng/mL
• 0%   = >10 ng/mL

Smoker

• 95% = <5.0 ng/mL
• 4%   = 5.1 to 10 ng/mL
• 1%   = >10 ng/mL

Source 2

• Adult (Non Smoker) = < 2.5 ng/ml
• Adult (Smoker) = < 5 ng/ml

Raised in benign conditions:

1. in cirrhosis (45%).
2. Pulmonary emphysema (30%).
3. Benign breast disease (15%).
4. Ulcerative colitis (15%).
5. Rectal polyp (5%).
6. pancreatitis.
7. smoking.
8. Inflammation.
9. Hypothyroidism.
10. Inflammatory bowel disease.
11. Peptic ulcer.

Raised in malignant condition:

1. colorectal cancer (70%).
   1. In Duke’s stage A 28%.
   2. In Duke’s stage B 45%.
2. Lung (45%).
3. breast cancer (40%).
4. Gastric carcinoma (50%).
5. Giant cell carcinoma of the thyroid.
6. Pancreatic cancer (55%).
7. Ovarian cancers (25%).
8. Uterine carcinoma (40%).

Important facts of CEA in Colon Carcinoma:

1. CEA level varies inversely with the grade, and well-differentiated tumor producing more CEA than poorly differentiated carcinoma.
2. This is not a reliable screening test for cancer. This is good to monitor the recurrence of colon cancer.
3. Pretreatment CEA level is a good indicator of tumor burden and prognosis.
   1. The preoperative level of >5 ng/mL is a poor prognostic indicator.
   2. After surgery, it should come to a normal level.
   3. Persistently raised level after surgery indicates the presence of the disease and need further workup.
4. patient with low or normal level has a limited disease than a high level indicating advanced disease and maybe with metastasis.
5. Drastically low level after surgery indicates almost complete cure of the tumor.
   1. If there are raised levels 5 times of the normal, then laparotomy is positive in 90% of the cases.
6. CEA is raised in only 25 % of cancer confined to the colon, 50 % positive nodes, and 75 % with distant metastasis.
7. Left-sided cancers have more raised CEA than right-sided tumors.
8. Bowel obstruction produces a higher level of CEA.
9. In the case of liver diseases, it’s level is raised because it’s metabolized in the liver.
10. Patient with a high level of preoperative CEA has a worse outcome than patient with low level.

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