Tumor Marker:- Part 4 – CA-Antigens, CA 15-3, CA 549, CA 27.29, CA 125, CA 19-9, CA 72-4
- Now there is a discussion of the following tumor markers.
- CA 15-3.
- CA 549.
- CA 125.
- CA 72-4
- CA 27.29.
- CA 19-9
Definition of Cancer antigen (CA antigen)
- The tumor marker is the carbohydrate antigen (CA) or cancer antigen (CA).
- These antigens are released by the tumor cells.
- These CA (cancer antigens) are released in the blood circulation, giving information about the tumor spread.
- These markers can also be increased in benign conditions, like infection or inflammation, or benign tumors.
CA 15-3 (Cancer antigen 15-3)
- These are abbreviated as CA for carbohydrate antigen or cancer antigen.
- This is detected by the use of two antibodies.
- Murine monoclonal antibody against the membrane-rich extract of human breast cancer metastasis to the liver.
- The second monoclonal antibody was developed against the human milk fat globule membrane.
- This tumor marker 15-3 is used to stage breast cancer and monitor the treatment.
- In <50% of the cases, the level is high in localized breast cancer or in the case of a small tumor.
- In the case of metastatic breast cancer, 80% of cases have raised CA-15-3 levels.
- For the screening of breast cancer, CA 15-3 is limited.
- CA 15-3 was the first breast tumor available.
- CA 15-3 is raised in benign breast diseases and other malignancies like lung, pancreas, ovary, and prostate.
- CA 15-3 is used not for the diagnosis but for monitoring the treatment effect.
The normal CA 15-3
- The upper limit is 25 kU/L.
An elevated level is seen in the following:
- Primary Breast cancer (23 %).
- Metastatic breast cancer (69 %).
- Pancreatic tumors (80 %).
- Lung tumors (70 %).
- Ovarian tumors (64 %).
- Colorectal tumors (64 %).
- Liver cancer (28 %).
Elevated level in Benign conditions like:
- Benign liver (42 %).
- Benign breast diseases (16 %).
CA 549 (Cancer antigen 549)
- This is an acidic glycoprotein abbreviated as CA from carbohydrate antigen.
- This is a carcinoma-associated mucin antigen, which is a tumor marker for breast cancer.
- It has two species with a molecular weight of 400 kD and 512 kD.
Normal CA 549
- In the healthy women population, 95% is below 11 kU/ L.
- Another source: The upper limit of normal was established as 15.5 U/mL.
Benign conditions when CA 549 is positive:
- Benign breast diseases.
- Benign liver diseases.
The malignant condition when CA 549 is positive:
- Metastatic carcinoma of:
- Ovary (50%).
- Lung (33 5).
- Prostate (40%).
- This is a better marker in the monitoring of breast carcinoma treatment.
Drawbacks of CA 549:
- CA 549 lacks the sensitivity and specificity to act as an effective screening tool.
- CA 549 is elevated in some pregnancies, liver diseases, and in benign breast diseases.
- It may be raised in the ovarian, lung, and even prostate cancers.
- 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)
- This is also the breast carcinoma marker.
- It is approved by the FDA.
- This is used for the staging of breast cancer and the monitoring of its treatment.
- In <50%, its level is high in localized breast cancer or in a small tumor burden.
- In the case of metastatic breast cancer, 65% show an elevated level.
- This test is not useful for the screening of breast cancer.
- It is useful in recurrent breast tumors in stages II and stages III.
- It is proven better than CA 15-3 in detecting recurrent breast cancer.
The normal level of CA 27-29
- <38 units/mL (<38 kU/L).
CA 125 (Cancer antigen 125)
Introduction of CA 125:
- This is a high molecular mass glycoprotein.
- This is recognized by the monoclonal antibody OC- 125.
- It has a 24% carbohydrate.
- Its physiological function is unknown.
Normal CA 125
- 0 to 35 units/mL (<35 kU/L).
- Another source: The normal level in the healthy population is up to 35 kU/L.
Response of CA 125 to treatment:
- CA 125 is a highly accurate tumor marker of a nonmucinous epithelial tumor of the ovary.
- It is raised in 80% of females with ovarian cancer.
- This tumor marker has high sensitivity and specificity for ovarian cancer.
- CA 125 is also used to determine the response of the patient to the treatment.
- The serial determination of CA 125, a progressive decrease in the value, indicates the response of the tumor to the treatment.
- A second look laparotomy will be positive in 97% of the patients where the CA 125 value is >35 units/mL.
- Whereas only 56% positive second-look laparotomy when the value is <35 units/mL.
- After two courses of chemotherapy, if there is a remarkable fall in the CA 125 value is a very good indicator of the response to chemotherapy. This is a good prognostic sign.
- In patients with a response to radiation, chemotherapy, or surgery, a delayed rise in the CA 125 level indicates recurrence in 93% of the patients.
- Raised in malignant conditions like:
- Ovarian carcinoma.
- Endometrial carcinoma.
- Pancreatic Tumors.
- Lung Tumors.
- Breast Tumors.
- Colorectal and other GI tract tumors.
- Peritoneal carcinomatosis.
- Benign conditions are in which is positive:
- The follicular phase of the menstrual cycle.
- Early pregnancy.
- Useful for the prognosis of endometrial carcinoma.
- This is not useful for screening for ovarian cancer.
- This can not be used to differentiate ovarian cancer from other malignancies.
- CA 125 is raised in ovarian cancers:
- 50 % positive in stage I.
- 90 % positive in stage II.
- > 90 % positive in stages III and IV.
- The increasing level of CA 125 correlates with the tumor size and staging.
- This can differentiate ovarian benign from malignant conditions.
- Postoperative falls in the level of CA 125 predict survival.
- CA 125 can help to diagnose the residual disease after the treatment.
- Persistent rise after the 3 cycles of chemotherapy indicates a poor prognosis.
- The detection of recurrent metastasis is 75% accurate.
CA 19-9 (Cancer antigen 19-9)
- This is glycolipid. This carbohydrate antigen exists on the surface of cancer cells.
- In serum, it exists as a mucin glycoprotein complex.
- This is synthesized by:
- Normal human pancreatic cells
- Biliary ductular cells.
- Gastric epithelial cells.
- Colon epithelial cells.
- Endometrial cells.
- Salivary gland epithelial cells.
CA 19-9 response to tumors:
- There is raised the level of CA 19-9 in pancreatic cancer compared to benign pancreatitis.
- If a patient has ascites, jaundice, and raised CA 19-9 level, there is the possibility of hepatobiliary cancer.
- CA 19-9 may not be raised in all cases of pancreatic cancer.
- Around 70% of pancreatic carcinoma and 65% of hepatobiliary cancer shows CA 19-9 elevated level.
- If the patient has a positive response to surgery or radiation, or chemotherapy, then there will be a decrease in the CA 19-9 level.
- A rapid rise in CA 19-9 level may be associated with recurrent or progressive tumor growth.
- 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.
- There is a very mild increase of CA 19-9 in cases of pancreatitis, gallstones, inflammatory bowel disease, cystic fibrosis, and cirrhosis.
Normal (Source 2):
- <37 units/L (<37 kU/L).
CA 19-9 increased level is seen in:
- Colorectal carcinoma (30 %).
- Pancreatic tumors(80 %).
- Hepatobiliary tumors (67 %).
- Stomach cancers (40 to 50 %).
- Hepatocellular carcinoma (30 to 50 %).
- Breast cancer (15 %).
CA 19-9 Useful for:
- In the monitoring of pancreatic and Colorectal carcinoma.
- 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)
- This is a marker of the GI tract and ovary.
- Elevated levels of CA 72-4 are found in gastric cancer.
- This is also raised in benign diseases like:
- Ovarian cyst.
Advantages of CA 72-4:
- CA 72-4 level after curative surgery of gastric cancer remains in the normal range.
- In 70% of the cases in recurrence, its level is increased prior to the clinical diagnosis.
- Along with CA 125, Ca- 72-4 increases the diagnostic value for ovarian cancer.
- There is a correlation between colorectal carcinoma with dukes classification.
CA 72-4 Positive in:
- Lung cancer (40 %).
- Ovarian cancer (36 %).
- GI tract cancer (6.7 %).
- Another source:
- 40% sensitivity for colorectal and gastric carcinoma diagnosis and overall 95% specificity.
- 50% sensitivity for ovarian cancer and overall 95% specificity.
|Test||marker for tumor|
|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.