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
Definition of CA antigen
- Carbohydrate antigen (CA) or cancer antigen is the tumor markers.
- These antigens are released by the tumor cells.
CA 15-3 (Carbohydrate antigen 15-3)
- These are abbreviated as CA for carbohydrate antigen.
- This is detected by the use of two antibodies.
- Murine monoclonal antibody against 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.
- The normal
- The upper limit is 25 kU/L.
- An elevated level is seen in:
- Primary Breast cancer (23 %).
- Metastatic breast cancer (69 %).
- Pancreatic tumors (80 %).
- Lung tumors (70 %).
- Ovarian tumors (64 %).
- Colorectal tumors (64 %).
- Liver cancer (28 %).
- Benign conditions like:
- Benign liver (42 %).
- Benign breast diseases (16 %).
- CA 15-3 is not used for the diagnosis but used for monitoring the treatment effect.
CA 549 (Carbohydrate antigen 549)
- This is 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.
- Benign conditions when positive:
- Pregnancy.
- Benign breast diseases.
- Benign liver diseases.
- The malignant condition when positive:
- Metastatic carcinoma of:
- ovary (50%).
- Lung (33 5).
- Prostate (40%).
- Breast
- Metastatic carcinoma of:
- This is a better marker in the monitoring of breast carcinoma treatment.
- Drawbacks of CA 549:
- CA 549 lacks the sensitivity and the specificity to act as an effective screening tool.
- CA 549 is elevated in some pregnancies, in liver diseases and benign breast diseases.
- It may be raised in 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.
- Normal:
- In healthy women population 95 % is below 11 kU/ L.
- Another source: The upper limit of normal established as 15.5 U/mL.
CA 27.29 (Carbohydrate 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% shows its elevated level.
- This test is not useful for the screening of breast cancer.
- It is useful in the recurrent breast tumor in stage II and stages III.
- It is proved better than CA 15-3 in the detection of recurrent breast cancer.
- Normal level (Source 2):
- <38 units/mL (<38 kU/L).
CA 125 (Carbohydrate antigen 125)
- CA 125 is a highly accurate tumor marker of a nonmucinous epithelial tumor of the ovary.
- It is raised in 80% of the females with ovarian cancer.
- This tumor marker has a high degree of sensitivity and specificity of 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 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 response to radiation or chemotherapy or surgery, if there is a delayed rise in the CA 125 level, it indicates recurrence in 93% of the patients.
- This is high molecular mass, glycoprotein.
- This is recognized by the monoclonal antibody OC- 125.
- IT has a 24% carbohydrate.
- Its physiological function is unknown.
- Raised in malignant conditions like:
- Ovarian carcinoma.
- Endometrial carcinoma.
- Pancreatic Tumors.
- Lung Tumors.
- Breast Tumors.
- Colorectal and other GI tract tumors.
- Lymphoma.
- Peritoneal carcinomatosis.
- Benign conditions are in which is positive:
- The follicular phase of the menstrual cycle.
- Cirrhosis.
- Hepatitis.
- Endometriosis.
- Pericarditis.
- Early pregnancy.
- Useful for the prognosis of endometrial carcinoma.
Important facts:
- This is not useful for screening of 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 stage III and IV.
- The increasing level of CA 125 correlates with the tumor size and staging.
- This can differentiate from ovarian benign from malignant conditions.
- Postoperative falls in the level of CA 125 predicts 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.
- In the detection of recurrent metastasis is 75% accurate.
- Normal (Source 2):
- 0 to 35 units/mL (<35 kU/L).
- Another source: The normal level in the healthy population is up to 35 kU/L.
CA 19-9 (Carbohydrate 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.
- There is raised the level of CA 19-9 in pancreatic cancer in comparison to benign pancreatitis.
- If a patient has ascites, jaundice and raised CA 19-9 level, then there is the possibility of hepatobiliary cancer.
- CA 19-9 may not be raised in all the 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.
- This is synthesized by:
- Normal human pancreatic cells
- Biliary ductular cells.
- Gastric epithelial cells.
- Colon epithelial cells.
- Endometrial cells.
- Salivary gland epithelial cells.
- This is a Marker for, and the 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 %).
- Useful in the monitoring of the 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.
- Normal (Source 2):
- <37 units/L (<37 kU/L).
CA 72-4 (Carbohydrate antigen 72-4)
- This is a marker of the GI tract and ovary.
- Elevated levels of CA 72-4 is found in gastric cancer.
- This is also raised in benign diseases like:
- Pneumonia.
- Pancreatitis.
- Cirrhosis.
- 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 of the colorectal carcinoma with dukes classification.
- CA 72-4 level after curative surgery of gastric cancer remains in the normal range.
- Positive in:
- lung cancer (40 %).
- Ovarian cancer (36 %).
- GI tract cancer (6.7 %).
- Another source:
- 40% sensitivity for the diagnosis of colorectal and gastric carcinoma and overall 95% specificity.
- 50% sensitivity for ovarian cancer and overall 95% specificity.
Tumor markers
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 |
- Please see in tumor marker part 1, 2 and 4