Tumor Marker:- Part 7 – CA 125 and CA 19-9 updated: May 14, 2023 by kamlesh kumar

Tumor Marker:- Part 7 – CA 125 and CA 19-9

updated: May 14, 2023 by kamlesh kumar 

Tumor Marker

CA 125

Sample For CA 125

• This test is done in the serum of the patient.
• No special preparation is needed.
• The serum can be stored for 24 hours at 2 to 8 °C. For a longer period, store at -20 °c.

Purpose Of The Test Of  CA 125

1. CA-125 is used as a tumor marker.
2. Most often, the CA-125 test is used to check the effect of treatment for ovarian cancer (for follow-up).
3. This is advised for the recurrence of ovarian tumors.
4. This test may be advised in a family with a strong history of ovarian cancer.
5. This may be advised if there is a BRCA1 or BRCA2 gene mutation.
6. It may be found in the Cancer of Breast and liver cell carcinoma.
7. It is also raised in pregnancy, cirrhosis, and peritonitis.
8. CA 125 is raised in non-mucinous epithelial ovarian tumors and has a major role in monitoring these tumors.

Definition Of CA 125  As A Tumor Marker

1. CA 125 glycoprotein (>200 kDa) is normally found in adult fallopian tubes, endocervix, and endometrium.
2. CA 125 is recognized by monoclonal antibodies (OC 125).
   1. It contains 24% carbohydrates.
   2. The physiologic function is unknown.
   3. This is not found in other tissues, even the ovary, lung, and breast tissue.
   4. But it appears in the tumors of ovarian carcinomas, adenocarcinoma of the cervix, and fallopian tubes.
3. Cancer antigen 125 (CA-125) is a cell surface glycoprotein (high mol. wt) first identified in the mucinous adenocarcinoma of the ovary.
4. This is also found in Adenocarcinoma of the cervix, endometrium, gastrointestinal tract carcinoma, and breast.

Origin of CA 125:

1. This is produced by the epithelial ovarian cancer cells, not the normal cells.
2. There is the greatest concentration of ovarian cancers.
   1. But this is also present in normal endometrial tissue, serous, and mucinous uterine fluids.
3. CA 125 measures the amount of this protein in the blood.
   1. CA-125 is found on the surface of many ovarian cancer cells and 80% of nonmucinous (usually serous carcinoma).
   2. It also can be found in other cancers and in small amounts in normal tissue.

CA 125 as a tumor marker:

1. CA 125 is the most useful tumor marker of ovarian cancer.
2. In a normal population upper limit of CA 125 is 35 KU/L.
3. CA 125 may be raised in non-ovarian cancers.
4. CA 125 is useful in advanced endometriosis.
5. CA 125 is not a good tumor marker for screening ovarian cancer in asymptomatic ladies.

CA 125 Interpretations:

1. A rising titer indicates a poor prognosis.
2. CA-125 may be found in liver diseases, acute Pancreatitis, Renal failure, lymphoma, and sometimes in normal females.
3. There are chances for high false-positive tests, so this is not used as a diagnostic but rather used for monitoring the disease.
4. Determine the baseline before starting the surgery or chemotherapy.
5. CA 125 is specific for ovarian cancers; It is an accurate marker for non-mucinous epithelial tumors of the ovary.
6. A second-time laparotomy will detect a tumor in 97 % of the patients with a CA-125 level of more than 3500 units/mL.
7. The rapid drop in CA 125 after two courses of chemotherapy is an excellent prognostic parameter.
8. If there is a tumor recurrence, the level rises again after 2 to 7 months.
9. This marker is raised in only 50% of the cases with stage 1 disease.
10. A total of 1 to 2% of the normal population has leveled more than 35 units /mL.
11. CA 125 may be raised in nonneoplastic abdominopelvic diseases like pregnancy, fibroids, benign ovarian cysts, pelvic inflammation, endometriosis, and ascites.
12. CA 125 may also be raised in non-ovarian tumors like the endometrium, fallopian tubes, pancreas, colon, and breast.

Stage of the ovarian cancer	% raised CA 125
Stage 1 disease	50% raised
Stage 2 disease	90% raised
Stage 3 disease	>90% raised
Stage 4	>90% raised

Normal CA 125

• 0 to 35 U/mL in 99 % of the female population (considered normal).
• Ca 125 < 65 U/mL in 100 % of the female population.
• CA 125 < 35 U/mL is considered normal.
• CA 125 > 65 U/mL has a positive predictive value for more than 95 % of ovarian cancers.

High Values In Noncancerous Conditions:

1. Some Benign noncancerous conditions may cause high levels of CA-125. These conditions include:
   1. Pelvic inflammatory disease (PID), endometriosis, uterine fibroids.
   2. Liver disease (such as hepatitis or cirrhosis).
   3. Pancreatitis,
   4. The first trimester of pregnancy and the menstrual cycle.

High Values In Cancerous Conditions:

1. Ovarian cancer or cancer in the fallopian tubes.
2. The cancer of the endometrium can cause high levels of CA-125.
3. Other types of cancer also may cause a high CA-125 level. These include:
   1. Cancer of the pancreas.
   2. Cancer of the stomach.
   3. Cancer of the esophagus.
   4. Liver cancers.
   5. Cancers of the breast.
   6. Cancers of the colon.
   7. Cancers of the lung.
4. In ovarian and endometrial carcinoma, the persistently rising values indicate progressive disease or poor therapeutic response.
   1. While declining values indicate a favorable prognosis and good therapeutic response.
5. Normal values do not rule out recurrence or the presence of an extensive tumor.
6. CA 125 has not proved to be a good screening test for ovarian cancer. This is elevated only in 50% of stage I disease.

CA- 19-9 (Cancer Antigen 19-9)

Sample For CA 19-9

1. This test needs venous blood to prepare the serum.
2. Can store serum at 2 to 8 C for 24 hours.
3. Freeze at -20 C if needed to store for more than 24 hours.

Purpose Of The Test Of CA 19-9

1. This is used as a tumor marker:
   1. It differentiates pancreatic cancer from pancreatitis.
   2. To monitor the treatment of pancreatic cancer.
   3. It helps to find the recurrence of pancreatic cancer.
   4. It is also advised for colorectal carcinoma.
2. Hepatobiliary cancer where is raised in 65% of the cases.
3. This is not specific or sensitive for the screening of the tumor.

Definition of  CA 19-9

1. This was initially isolated from colorectal carcinoma.
2. CA 19-9 is a cell surface antigen as a carbohydrate. It is glycolipids that is sialylated lactose-N-fucopentose II ganglioside.
   1. Chemically it is mucin-glycoprotein related or is identical to the Lewis blood group.

Location of CA 19-9

1. This is present in serum as mucin and in tissues as mono sial gangliosides.
   1. This is found in the normal epithelium of the pancreas, gallbladder, prostate, and stomach.
2. Ca 19-9 is released from the surface of the cancer cells and enters the blood.
3. Initially, it was considered for colorectal tumors.

CA 19-9 interpretations

1. In pancreatic mass with biliary obstruction and a raised level of CA 19-9 favors the diagnosis of pancreatic cancer.
   1. This is elevated in 80% of pancreatic cancer.
2. In hepatobiliary cancers, the patient may have ascites, jaundice, and raised CA 19-9 level.
3. In pancreatic cancers, it is raised in 70% of the cases, and in hepatobiliary is 65%.
4. Its level will decrease in good response to surgical, radiation, or chemotherapy treatment.
5. The rapid rise indicates the recurrence or rapid growth of the tumor.

The mild raised level is seen in the following:

1. Stomach cancer.
2. Colorectal cancer.
3. Hepatoma.

There is a mild increase in patients with:

1. Pancreatitis.
2. Gallstones.
3. Cirrhosis.
4. Inflammatory bowel disease.
5. Cystic fibrosis.

Normal CA 19-9

• < 37 U /mL or < 37 k units /L .
• One reference says = <70 U/mL
• > 1000 U /mL had a sensitivity of 41% and specificity of 99.8%.

Raised level of CA 19-9 seen in:

1. Pancreatic cancers.
2. Pancreatitis.
3. Hepatobiliary Carcinoma.
4. Colorectal cancer.
5. Stomach cancer.
6. Lung cancer.
7. Ovarian cancers
8. Esophageal cancers.

Other benign conditions with raised levels of CA 19-9 are:

1. Cholecystitis.
2. Gallstones.
3. Cirrhosis.
4. Inflammatory bowel disease.
5. Autoimmune disease.
6. Liver cirrhosis.
7. Cystic fibrosis.
8. Thyroid disease.
9. Cholangitis.

• CA 19-9 is less efficient than CEA for monitoring colorectal carcinoma.
• Ca-19-9 is efficient for monitoring pancreatic carcinoma.