Tumor Markers

• Now, we will discuss the following tumor markers.
  1. CA 15-3.
  2. CA 549.
  3. CA 125.
  4. CA 72-4
  5. CA 27.29.
  6. CA 19-9

Cancer antigen (CA-antigen)

How will you define cancer antigen (CA antigen)?

1. The tumor marker is the carbohydrate antigen (CA) or cancer antigen (CA).
2. These antigens are released by the tumor cells.
3. Carcinoma antigens (CAs) are tumor markers that detect, monitor, and evaluate certain types of cancers. They are proteins, glycoproteins, or other molecules produced by cancer cells or the body in response to cancer.
4. These CA (cancer antigens) are released in the blood circulation, giving information about the tumor spread.
5. These markers can also be increased in benign conditions, like infection, inflammation, or tumors.
6. These are abbreviated as CA for carbohydrate antigen or cancer antigen.
7. The use of two antibodies detects this:
   1. Murine monoclonal antibody against the membrane-rich extract of human breast cancer metastasis to the liver.
   2. The second monoclonal antibody was developed against the human milk fat globule membrane.

CA 15-3 (Cancer antigen 15-3)

What is the role of CA 15-3?

1. This tumor marker 15-3 is used to stage breast cancer and monitor the treatment.
2. In <50% of the cases, the level is high in localized breast cancer or the case of a small tumor.
3. In the case of metastatic breast cancer, 80% of cases have raised CA-15-3 levels.
4. For breast cancer screening, CA 15-3 is a limited value.
5. CA 15-3 was the first breast tumor antigen available.
6. CA 15-3 is raised in benign breast diseases and other malignancies like lung, pancreas, ovary, and prostate.
7. CA 15-3 is used not for the diagnosis but for monitoring the treatment effect.

What is the normal CA 15-3?

1. The upper limit is 25 kU/L.

What are the causes of increased CA 15-3?

1. Primary Breast cancer (23 %).
2. Metastatic breast cancer (69 %).
3. Pancreatic tumors (80 %).
4. Lung tumors (70 %).
5. Ovarian tumors (64 %).
6. Colorectal tumors (64 %).
7. Liver cancer (28 %).

What are the causes of increased CA 15-3 in benign conditions?

1. Benign liver (42 %).
2. Benign breast diseases (16 %).

CA 549 (Cancer Antigen 549)

1. This is an acidic glycoprotein abbreviated as CA from carbohydrate antigen.
2. This is a carcinoma-associated mucin antigen, which is a tumor marker for breast cancer.
3. It has two species with a molecular weight of 400 kD and 512 kD.

What is the normal value of CA 549?

1. In the healthy women population, 95% is below 11 kU/ L.
2. Another source: The upper limit of normal was established as 15.5 U/mL.

What are the benign conditions when CA 549 is positive?

1. Pregnancy.
2. Benign breast diseases.
3. Benign liver diseases.

What are the causes of positive CA 549?

1. Metastatic carcinoma of:
   1. Ovary (50%).
   2. Lung (33 5%).
   3. Prostate (40%).
   4. Breast
2. This is a better marker for monitoring breast carcinoma treatment.

What are the drawbacks of CA 549?

1.  CA 549 lacks the sensitivity and specificity to act as an effective screening tool.
2. CA 549 is elevated in some pregnancies, liver diseases, and benign breast diseases.
3. It may be raised in ovarian, lung, and even prostate cancers.
4. It has limited value in detecting early breast cancer because of its low values in the early stages of breast cancer.

CA 27.29 (Cancer antigen 27.29)

1. This is also the breast carcinoma marker.
   1. The level of CA 27.29, also known as 27.29, is used as a tumor marker to measure the activity of the disease in patients with breast carcinoma.
2. The FDA approves it.
3. This is used for the staging of breast cancer and the monitoring of its treatment.
4. In <50%, its level is high in localized breast cancer or in a small tumor burden.
5. In the case of metastatic breast cancer, 65% show an elevated level.
6. This test is not useful for the screening of breast cancer.
7. It is useful in recurrent breast tumors in stages II and stages III.
8. It is proven better than CA 15-3 in detecting recurrent breast cancer.

The normal level of CA 27-29

1. <38 units/mL (<38 kU/L).

CA 125 (Cancer antigen 125)

What are the introductions for CA 125?

1. CA 125 is a highly accurate tumor marker of a nonmucinous epithelial tumor of the ovary.

How will you define CA 125?

1. This is a high molecular mass glycoprotein.
2. This is recognized by the monoclonal antibody OC- 125.
3. It has a 24% carbohydrate.
4. Its physiological function is unknown.

What is normal CA 125?

1. 0 to 35 units/mL (<35 kU/L).
2. Another source: The normal level in the healthy population is up to 35 kU/L.

What is the response of  CA 125 to treatment?

1. It is raised in 80% of females with ovarian cancer.
2. This tumor marker has high sensitivity and specificity for ovarian cancer.
3. CA 125 is also used to determine the patient’s response to the treatment.
4. The serial determination of CA 125, a progressive decrease in the value, indicates the tumor’s response to the treatment.
5. A second-look laparotomy will be positive in 97% of patients whose CA 125 value is >35 units/mL.
6. Whereas only 56% positive second-look laparotomy when the value is <35 units/mL.
7. If the CA 125 value remarkably falls after two courses of chemotherapy, this is a very good indicator of the response to chemotherapy and a good prognostic sign.
8. In patients who respond to radiation, chemotherapy, or surgery, a delayed rise in the CA 125 level indicates recurrence in 93% of the patients.

What are the causes of increased CA 125 value in malignant conditions?

1. Ovarian carcinoma.
2. Endometrial carcinoma.
3. Pancreatic Tumors.
4. Lung Tumors.
5. Breast Tumors.
6. Colorectal and other GI tract tumors.
7. Lymphoma.
8. Peritoneal carcinomatosis.

What are the Benign conditions where CA 125 is positive?

1. The follicular phase of the menstrual cycle.
2. Cirrhosis.
3. Hepatitis.
4. Endometriosis.
5. Pericarditis.
6. Early pregnancy.
   1. Useful for the prognosis of endometrial carcinoma.

What are the Important facts about CA 125?

1. This is not useful for screening for ovarian cancer.
2. This can not be used to differentiate ovarian cancer from other malignancies.
3. CA 125 is raised in ovarian cancers:
   1. 50 % positive in stage I.
   2. 90 % positive in stage II.
   3. > 90 % positive in stages III and IV.
4. The increasing level of CA 125 correlates with the tumor size and staging.
5. This can differentiate benign ovarian conditions from malignant ones.
6. Postoperative falls in the level of CA 125 predict survival.
7. CA 125 can help to diagnose the residual disease after the treatment.
8. Persistent rise after the three cycles of chemotherapy indicates a poor prognosis.
9. The detection of recurrent metastasis is 75% accurate.

CA 19-9 (Cancer antigen 19-9)

How will you define CA 19-9?

1. This is glycolipid. This carbohydrate antigen exists on the surface of cancer cells.
   1. In serum, it exists as a mucin glycoprotein complex.
2. This is synthesized by:
   1. Normal human pancreatic cells.
   2. Biliary ductular cells.
   3. Gastric epithelial cells.
   4. Colon epithelial cells.
   5. Endometrial cells.
   6. Salivary gland epithelial cells.

What is the response of the CA 19-9 to tumors?

1. There is a rise in the level of CA 19-9 in pancreatic cancer compared to benign pancreatitis.
2. If a patient has ascites, jaundice, and raised CA 19-9 level, there is the possibility of hepatobiliary cancer.
3. CA 19-9 may not be raised in all cases of pancreatic cancer.
   1. Around 70% of pancreatic carcinoma and 65% of hepatobiliary cancer show CA 19-9 elevated levels.
4. If the patient has a positive response to surgery, radiation, or chemotherapy, the CA 19-9 level will decrease.
   1. A rapid rise in CA 19-9 level may be associated with recurrent or progressive tumor growth.
5. There may be a mild raised level of CA 19-9 in gastric cancer, colorectal cancer, hepatoma, and 6% to 7% of non-gastrointestinal cancers.
6. There is a very mild increase of CA 19-9 in cases of pancreatitis, gallstones, inflammatory bowel disease, cystic fibrosis, and cirrhosis.

What is the normal CA 19-9?

Source 2

1. <37 units/L  (<37 kU/L).

What are the causes of raised CA 19-9?

1. Colorectal carcinoma (30%).
2. Pancreatic tumors(80%).
3. Hepatobiliary tumors (67%).
4. Stomach cancers (40% to 50%).
5. Hepatocellular carcinoma (30% to 50 %).
6. Breast cancer (15 %).

What are the uses of CA 19-9?

1. In the monitoring of pancreatic and Colorectal carcinoma.
2. CA 19-9 is a tumor marker for diagnosis and response to treatment and the surveillance of pancreatic or hepatobiliary cancers.

CA 72-4 (Cancer antigen 72-4)

1. This is a marker of the GI tract and ovary.
   1. Elevated levels of CA 72-4 are found in gastric cancer.
2. This is also raised in benign diseases like:
   1. Pneumonia.
   2. Pancreatitis.
   3. Cirrhosis.
   4. Ovarian cyst.

What are the advantages of CA 72-4?

1. CA 72-4 level after curative surgery of gastric cancer remains in the normal range.
   1. In 70% of the cases in recurrence, its level is increased before the clinical diagnosis.
2. Along with CA 125, CA 72-4 increases the diagnostic value for ovarian cancer.
3. There is a correlation between colorectal carcinoma and Duke classification.

What are the causes of CA 72-4 Positivity?

1. Lung cancer (40%).
2. Ovarian cancer (36%).
3. GI tract cancer (6.7%).
4. Another source:
   1. 40% sensitivity for colorectal and gastric carcinoma diagnosis and overall 95% specificity.
   2. 50% sensitivity for ovarian cancer and overall 95% specificity.

Tumor markers

Test	Tumor markers
CA 125	Ovarian carcinoma
CA- 549	Breast cancer
CA 15-3	Breast cancer
CA 72-4	Gastric carcinoma
CA 19-9	Pancreatic carcinoma

Questions and answers:

• Please see tumor markers parts 1, 2, and 4.

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