Carcinoembryonic Antigen (CEA)

What sample is needed for Carcinoembryonic Antigen (CEA)?

1. This test is done on the patient’s serum.
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, will indicate tumor metastasis.

What are the precautions for Carcinoembryonic Antigen (CEA)?

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

What are the Indications for Carcinoembryonic Antigen (CEA)?

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

How will you define Carcinoembryonic Antigen (CEA)?

1. History of CEA:
   1. CEA was discovered in 1965 by Gold and Freeman.
   2. This experiment was done by immunizing rabbits with human colon cancer cell extract.
   3. This was found in the serum of a patient with colorectal carcinoma.
   4. The antigen, which was found in embryonic tissue, was named carcinoembryonic antigen.
2. Normal function of CEA:
   1. In adults, there is a minimal function, and present in very low amounts.
   2. In the fetus, CEA functions as a cell adhesion molecule.
3. Thus, this CEA antigen was considered the indicator of colorectal cancers.
4. Later on, it was found in other various tumors like breast, stomach, pancreas, hepatobiliary tumors, and sarcomas.
5. This was also found in benign conditions like ulcerative colitis, cirrhosis, and diverticulitis.
6. Chronic smokers also have raised the level of CEA.
7. Carcinoembryonic Antigen (CEA) indicates the bulk of the tumor.

What is the structure of the Carcinoembryonic Antigen (CEA)?

1. The tissue found in embryonic tissue is called carcinoembryonic antigen (CEA).
2. CEA is normally found in the fetal gut tissue.
3. By the time the detectable birth level of CEA disappears.
4. There are about 10 genes located on chromosome 19 that encode the CEA protein.
5. This is a glycoprotein with a molecular weight of 150 to 300 kD.
   1. It contains 45% to 55% carbohydrates.
   2. It is a single polypeptide chain consisting of 641 amino acids, with lysine at its N-terminal.
   3. CEA proteins are encoded by 10 genes located on chromosome 19.
   4. CEA is a part of the immunoglobulin gene ” superfamily.”

6. CEA is a tumor-associated, oncofetal antigen seen in embryonic and fetal tissue.
7. CEA is a glycoprotein that normally occurs in fetal gut tissue.

How will you interpret Carcinoembryonic Antigen (CEA)?

1. CEA is increased in:
   1. Colorectal cancer = 70%.
   2. Gastric = 50%.
   3. Pancreatic = 55%.
   4. Lung = 45%.
   5. Breast = 40%.
   6. Ovarian = 25%.
   7. Uterine = 40%
   8. CEA is not used to screen for cancers.
   9. This is more specific for colorectal carcinoma.

2. 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.
3. CEA is less commonly increased in lymphoma, leukemia, and malignant melanoma.
4. CEA has also been seen in an HIV-positive patient with P.C.carinii, a heavy smoker, and inflammatory bowel disease.
5. This is metabolized in the liver, so in liver diseases, it is increased.
6. Its median value is higher for smokers than non-smokers.
7. It is useful for monitoring GIT cancer, especially colorectal carcinoma.
8. CEA is increased by 60% to 90% of metastasis of lung cancer.
9. If the CEA level increases from the baseline after surgery, it indicates the tumor’s recurrence.
10. Patients with high preoperative concentration have a poorer prognosis than those with low values.

What is the role of Carcinoembryonic Antigen (CEA) in colon cancer?

1. After the surgery and removal of colon cancer, CEA takes 6 to 12 weeks to become normal.
2. Failure to become normal suggests incomplete surgery for colon cancer.
3. A progressive increase in the CEA indicates the recurrence of colon cancer.
4. Monitor the patient by estimating CEA every 2 to 3 months in stage II and stage III colon cancer cases for 2 or more years.
5. What is the effect of CEA on staging?
   1. Increased concentration of CEA (>3 ng/mL) indicates a poor prognosis in that stage of the tumor-like:
   2. In Dukes, stage A = 28%.
   3. Dukes stage B = 45%
   4. Dukes stage C = 70%
6. Before therapy, CEA <5 ng/mL suggests localized disease and a favorable prognosis.
7. CEA >10 ng/mL suggests advanced disease and poor prognosis.
8. If CEA is >20 ng/mL, 80% of patients have a recurrence within 14 months after surgery.
9. The pattern of CEA changes during chemotherapy.
10. CEA response to therapy:
    1. If there is no decrease in the CEA level with therapy, indicating the unresponsiveness of the tumor.
    2. In case of a decrease, indicate a responsive tumor.
    3. If there is a surge of CEA for weeks followed by a decrease in the level, it indicates a responsive tumor.
    4. An immediate decrease in CEA followed by an increase indicates an unresponsive tumor.

What are the drawbacks of Carcinoembryonic Antigen (CEA)?

1. CEA can be detected in benign and malignant conditions.
   1. CEA is not produced in undifferentiated cancer.
   2. 30% of metastatic colon cancer has no increased CEA level.
2. CEA is not raised in all colorectal cancers. Therefore, it is not a reliable screening test.
3. Its use is limited to knowing the prognosis and monitoring the tumor response to antineoplastic therapy in patients with cancer.
4. CEA is helpful in patients with breast and gastrointestinal malignancies.

What is the normal Carcinoembryonic Antigen (CEA)?

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

What is the use of CEA testing?

1. Diagnosis:
   1. It can be used as a diagnostic test along with other workups of the patients.
2. Monitoring of the tumor:
   1. It is used to monitor the treatment response.
   2. It can detect recurrence after the treatment.
3. Prognosis:
   1. A raised level of CEA indicates an advanced disease or poor prognosis.
4. CEA is also useful for monitoring breast, lung, gastric and pancreatic carcinoma.
5. Early diagnosis of breast cancer does not elevate CEA.

What are the causes of raised Carcinoembryonic Antigen (CEA) 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.

What are the causes of raised Carcinoembryonic Antigen (CEA) in malignant conditions?

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%).

What are the important facts about Carcinoembryonic Antigen (CEA) in colon cancer?

1. CEA level varies inversely with the grade, and well-differentiated tumors produce more CEA than poorly differentiated carcinoma.
2. This is not a reliable screening test for cancer. This is good for monitoring 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 levels after surgery indicate the presence of the disease and need further workup.
4. Patient with a lower or normal level has a lower disease than a high level, indicating advanced disease and maybe metastasis.
5. A drastically low level after surgery indicates an almost complete cure for the tumor.
   1. If raised levels are 5 times 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, its level is raised because it’s metabolized in the liver.
10. A patient with a high preoperative CEA level has a worse outcome than a low level.

• Note: Our findings are from different sources.

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