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How Do Tumor Markers Work? - page 2

Examples of tumor markers

The alphabetical list of tumor markers that follows is from the American Cancer Society (ACS) and summarizes specific tumor markers listed in their December 2008 publication Tumor Markers. According to the ACS, the following tumor markers are the most commonly used today. These marker levels listed may also be checked in other types of cancer that are not listed.

The ACS states that different labs may consider slightly different marker levels to be normal or abnormal depending on various factors such as age, gender, the specific 8 test kit, and testing techniques. The values listed here are average values and most labs will list their own reference ranges for comparison when providing their test results.

This list will change often as the science is moving fast. Please go to the American Cancer Society website and search for tumor markers to get the latest version.

Alphabetical List (not inclusive)

Alpha-Fetoprotein (AFP)

AFP is elevated in liver cancer. Normal levels of AFP are usually less than 10 ng/mL (nanograms/milliliter). AFP levels are increased in most patients with liver cancer. In someone with a liver tumor, an AFP level over a certain value indicates that the person has liver cancer.

In people without liver problems, that value is 400 ng/mL. But in a person with chronic hepatitis who has a liver tumor, AFP levels of over 4,000 ng/mL are a sign of liver cancer.

AFP is also useful in following the response to treatment for liver cancer. If the cancer is completely removed with surgery, the AFP level should go down to normal. If the level goes back up again, it often means that the cancer has come back.

AFP level is also higher in testicular cancers of embryonic cell and endodermis sinus types and is used for follow-up of these cancers. Elevated AFP levels are also seen in certain rare types of ovarian cancer such as yolk sac tumor or mixed germ cell cancer.

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Beta-2-Microglobulin (B2M)

B2M blood levels are elevated in multiple myeloma, chronic lymphocytic leukemia (CLL), and some lymphomas. Levels may also be higher in some non-cancerous conditions, such as kidney disease.

Normal levels are usually below 2.5 mg/L (milligrams/liter). B2M is useful to help predict the long-term outlook in some of these cancers. Patients with higher levels of B2M usually have a poorer prognosis. B2M is also checked during treatment of multiple myeloma to see how well the treatment is working.



See human chorionic gonadotropin (HCG)


Bladder Tumor Antigen (BTA)

BTA is found in the urine of many patients with bladder cancer. It may also be associated with non-cancerous conditions such as kidney stones or urinary tract infections. Test results are reported as either positive (BTA is present) or negative (BTA is not present). It is sometimes used along with NMP22 to test patients for bladder cancer recurrence. This test is not widely used and still being studied, and not considered as reliable as cystoscopy for diagnosing bladder cancer. But, it may be helpful in allowing fewer cystoscopies during bladder cancer follow-up. Most experts consider cystoscopy the standard for diagnosis and follow-up of bladder cancer.


CA 15-3

CA 15-3 is used most often to monitor people with breast cancer. Elevated blood levels are found in less than 10% of patients with early disease and in about 70% of patients with advanced disease. Levels usually drop after effective treatment. However they may increase in the first few weeks after treatment is started due to dying cancer cells in the bloodstream. The normal level is usually less than 30 U/mL (units/milliliter) depending on the lab used for the test. But levels as high as 100 U/mL can sometimes be seen in women who do not have cancer. Levels of this marker can also be higher in other cancers and in some non-cancerous conditions such as benign breast conditions and hepatitis.


CA 27.29

CA 27.29 is another marker that can be used to monitor people with breast cancer during or after treatment. This test measures the same marker as the CA 15-3 test, but in a different way. Although CA 27.29 is a newer test than CA 15-3, it is not better in detecting either early or advanced disease, but it may be less likely to be positive in cases of people without cancer. The normal level is usually less than 40 U/mL (units/milliliter) depending on the testing lab. This marker can also be elevated in the presence of other cancers and in some non-cancerous conditions, but it is not elevated in all patients with breast cancer.


CA 125

CA 125 is the standard tumor marker used to follow women during or after treatment for epithelial ovarian cancer. Normal blood levels are usually less than 35 U/mL (units/milliliter). More than 90% of women have high levels of CA 125 when ovarian cancer is advanced. CA 125 levels are monitored during treatment to evaluate responsiveness. Levels are also elevated in about half of women whose cancer has not spread outside the ovary. Studies suggest that CA 125 can miss many early stage ovarian cancers. Other conditions can cause an elevated CA 125 level, including fibroids, endometriosis, lung, pancreatic, breast, and colon cancer, and a cancer history. Since ovarian cancer is a rather rare disease, an increased CA 125 level is more likely to be caused by something other than ovarian cancer.


CA 72-4

CA 72-4 is a newer test being studied for use in ovarian and pancreatic cancer and in cancers originating in the digestive tract, especially stomach cancer. There is no evidence that it is better than the tumor markers currently in use, but it may be valuable when used along with other tests. Studies of this marker are still in progress.


CA 19-9

The CA 19-9 test was first developed to detect colorectal cancer, but it is more often used in patients with pancreatic cancer. In very early disease stage the level is often normal, and therefore it is not reliable as a screening test. However, CA 19-9 is the best tumor marker for following patients with cancer of the pancreas. Normal blood levels of CA 19-9 are below 37 U/mL (units/milliliter). A high CA 19-9 level in a newly diagnosed patient usually means the disease is advanced. CA 19-9 can be used to monitor colorectal cancer, but the CEA test is preferred for that cancer. CA 19-9 can also be elevated in other forms of digestive tract cancer, especially cancers of the stomach and bile ducts, and in some non-cancerous conditions such as thyroid disease and pancreatitis.



Calcitonin is a hormone produced by cells called parafollicular C cells in the thyroid gland that usually helps regulate blood calcium levels. Normal calcitonin levels are from below 5 to 12 pg/ml (picograms/milliliter). In cases of medullary thyroid carcinoma (MTC), a rare cancer that starts in the parafollicular C cells, blood levels of this hormone are often greater than 100 pg/ml.

Calcitonin is one of the rare tumor markers that can be used to help detect earlystage cancer. Because MTC is often inherited, blood calcitonin can be measured to detect the cancer in its very earliest stages in family members who known to be at risk. Other cancers, such as lung cancers and leukemias, can also cause calcitonin levels to be elevated, but it is not usually used to follow these types of cancers.


Carcinoembryonic antigen (CEA)

CEA is not used to diagnose or screen for colorectal cancer, but it is the preferred tumor marker to help predict prognosis in patients with colorectal cancer. The normal range of blood levels varies from lab to lab, but levels higher than 3 ng/mL (nanograms/milliliter) are not normal. The higher the CEA level at the time colorectal cancer is detected, the more likely it is that the cancer is advanced. CEA is also the standard marker used to monitor colorectal cancer patient response during and after treatment. This marker can be high in other cancers, including lung, breast, thyroid, pancreas, liver, stomach, prostate, ovary, and bladder. CEA levels are elevated in patients with some non-cancerous diseases and also in otherwise healthy smokers, too.


Chromogranin A (CgA)

CgA isproduced by neuroendocrine tumors, which include carcinoid tumors, neuroblastoma, and small cell lung cancer. The blood level of CgA is often elevated in people with these diseases and considered the most sensitive tumor marker for carcinoid tumors. CgA is abnormal in 1 out of 3 people with localized disease and 2 out of 3 of those with cancer that has metastasized. Levels can also be elevated in some advanced forms of prostate cancer that have neuroendocrine features. The range of normal blood levels varies depending on the testing centers used, but is commonly less than 50 ng/mL (nanograms/milliliter).


Hormone Receptors

Breast tumor tissue samples for all cases of breast cancer are tested for estrogen and progesterone receptors. Breast cancers that contain estrogen receptors are often referred to as "ER-positive." Those with progesterone receptors are "PR-positive." About 2 out of 3 breast cancers test positive for at least one of these markers. These cancers tend to grow more slowly and have a better outlook than cancers without these receptors. Cancers that have these receptors can be treated with hormone therapy such as tamoxifen or aromatase inhibitors.


HER2 (also known as HER2/neu, erbB-2, or EGFR2)

HER2 is a protein that supports breast cancer cell growth and is elevated in some breast cancers. Higher-than-normal levels can also be found in other cancers. The HER2 level is usually found by testing a sample of the cancer tissue itself instead of the blood. About 1 in 5 breast cancers test positive for HER2. These cancers tend to grow and spread more aggressively than other breast cancers so all newly diagnosed breast cancers should be tested for HER2. HER2-positive cancers are more likely to respond to certain treatments such as trastuzumab (Herceptin®) and lapatinib (Tykerb®) that work against the HER2 receptor on breast cancer cells.


Human Chorionic Gonadotropin (HCG)

HCG (also known as beta-HCG) blood levels are elevated in patients with some types of testicular and ovarian cancers (germ cell tumors). HCG levels are also higher in some patients with mediastinal germ cell tumors- cancers in the middle of the chest that start in the same cells as germ cell tumors of the testicles and ovaries. Levels of HCG can be used to help diagnose these conditions, monitor treatment efficacy, and detect recurrence. It is hard to define the HCG normal level because there are different ways to test for this marker and each has its own normal value.



As opposed to tumor markers, immunoglobulins are antibodies in the form of blood proteins normally made by immune system cells to help fight germs. There are many types of immunoglobulins, including IgA, IgG, IgD, and IgM. Bone marrow cancers such as multiple myeloma and Waldenstrom macroglobulinemia often cause a person to have too much of one type of immunoglobulin in the blood. These cancers can also cause pieces of immunoglobulin to be found in the urine. A high level of immunoglobulins may be a sign of one of these diseases.

A test called serum protein electrophoresis (also called SPEP) evaluates immunoglobulins. This test uses an electrical current to separate the blood proteins. In cases of myeloma or macroglobulinemia, the monoclonal immunoglobulin forms a monoclonal "spike" on the SPEP. This is often called the M spike, monoclonal protein, or M protein. The level of the spike is important since some people may show low levels of a spike without having myeloma or macroglobulinemia. The diagnosis of multiple myeloma or Waldenstrom macroglobulinemia must be confirmed by a biopsy of the bone marrow. Immunoglobulin levels can also be monitored to evaluate treatment efficacy for these diagnoses.


Lipid Associated Sialic Acid in Plasma (LASA-P)

LASA-P has been studied as a marker for ovarian cancer and other cancers. For the most part it has not proven valuable, and has been replaced by more specific marker tests. It is not specific for any one cancer or even for cancer in general since it can be elevated in some non-cancerous conditions. LASA-P is used together with other tumor markers to follow response to treatment.


Neuron-Specific Enolase (NSE)

NSE, like chromogranin A, is a marker for neuroendocrine tumors such as small cell lung cancer, neuroblastoma, and carcinoid tumors. It is not used as a screening test. It is most useful in the follow-up of patients with small cell lung cancer or neuroblastoma. Chromogranin A seems to be a better marker for carcinoid tumors. Elevated levels of NSE may also be found in some non-neuroendocrine cancers. Abnormal levels are usually higher than 9 ug/mL (micrograms/milliliter).



NMP22 is a protein found in the nucleus of cells. Levels of NMP22 are often elevated to more than 10 U/mL (units/milliliter) in the urine of people with bladder cancer. Current research indicates it is not sensitive enough to be used as a screening tool thus it is most often used to assess cancer recurrence after treatments as a less invasive way to look for cancer than cystoscopy. However it is not always accurate. NMP22 testing cannot replace of cystoscopy completely, but it can permit this procedure to be done less frequently. NMP22 levels can also be higher than normal in some non-cancerous conditions or after recent treatment with chemotherapy.


Prostate-Specific Antigen (PSA)

PSA is a tumor marker for prostate cancer. It is the only marker used to screen for prostate cancer, although its use is controversial since the marker is not always reliable and prostate cancer overtreatment is very common.

PSA is a protein made by cells of the prostate gland. The prostate gland is found only in men and it makes some of the liquid in semen. When the PSA test is used for screening, a digital rectal exam should also be performed.

The level of PSA in the blood can be elevated because of prostate cancer, but levels can also be affected by other factors. Men with benign prostatic hyperplasia (BPH), a non-cancerous growth of the prostate, often have higher levels. The PSA level also tends to be higher in older men and those with infected or inflamed prostates. It can also be elevated for a day or two after ejaculation.

PSA is measured in nanograms per milliliter (ng/mL). Most doctors feel that a blood PSA level below 4 ng/mL suggests cancer is unlikely. Levels greater than 10 ng/mL indicate cancer is likely. The significance of values between 4 and 10 is unclear. Men with PSA levels in this borderline range have about a 1 in 4 chance of having prostate cancer. Doctors often recommend a prostate biopsy for men with a PSA level above 4 ng/mL although there is disagreement with these assessment guidelines.

Some men with prostate cancer do not have an elevated PSA level, while others with a borderline or elevated level do not have cancer. Research indicates it may more useful to track the PSA level over time because an increase from one year to the next (called velocity) may suggest prostate cancer is more likely. A PSA baseline should be established at age 40, 45, 50, and then annually thereafter. Another strategy is to measure the PSA at least three times over a period of at least 18 months in order to get an accurate PSA velocity. Studies are evaluating how to optimize the use of PSA levels in prostate cancer diagnosis.

It can be helpful to measure the free PSA (or percent-free PSA) when a PSA value is in the borderline range (between 4 and 10 ng/mL) is to measure the free PSA (or percent-free PSA). PSA is in the blood in two forms- some is bound to a protein and some is free (freely circulating). The percent-free PSA (fPSA) is the ratio of how much PSA circulates free compared to the total PSA level. As the amount of free PSA goes up, the less likely it is that there is prostate cancer. When the free PSA makes up more than 25% of the total PSA, prostate cancer is unlikely. If the free PSA is below 10%, the chance of prostate cancer is much higher and it is recommended that a biopsy should be performed.

The PSA test is used in the follow-up of men with prostate cancer. For those who have been treated with surgery meant to cure the disease, the PSA should fall to an undetectable level. Those treated with radiation therapy should also have the PSA decrease after treatment. A rise in the PSA level may be a sign the cancer is recurring.


Prostatic Acid Phosphatase (PAP)

PAP (not to be confused with the Pap test for women) is another test that is used to check for prostate cancer. It was used before the development of the PSA test but is not used now because the PSA test is better.


Prostate-Specific Membrane Antigen (PSMA)

PSMA is a substance found in all prostate cells. Blood levels increase with age and in the presence of prostate cancer. PSMA is a very sensitive marker, but current research suggests it may be no better than using PSA. Its current use is limited to one element of a nuclear scan looking for the spread of prostate cancer in the body. Some potential immunotherapy treatments for prostate cancer based on PSMA are now being studied.



S-100 is a protein found in most melanoma cells. Tissue samples of suspected melanomas are often tested for this marker to help in diagnosis. 14 Some studies have shown that blood levels of S-100 are elevated in most patients with metastatic melanoma. The test is sometimes used to evaluate melanoma metastasis before, during, or after treatment.



TA-90 is a protein found on the outer surface of melanoma cells. As with S-100, TA- 90 can be used to assess the spread of melanoma. Its value in following melanoma patients is still being studied, and it is not widely used at this time. TA-90 is also being studied for use in checking the progress of other cancers such as colon and breast cancer.



Thyroglobulin is a protein made by the thyroid gland. Normal blood levels depend on age and gender: thyroglobulin levels are elevated in many thyroid diseases, including some common forms of thyroid cancer. Thyroglobulin levels in the blood should fall to undetectable levels after treatment. A rise in the thyroglobulin level may mean the cancer has returned. In people with thyroid cancer that has spread, thyroglobulin levels can be monitored to assess efficacy of treatments. Some people's immune systems make antibodies against thyroglobulin, which can affect test result and is why levels of anti-thyroglobulin antibodies are often measured at the same time.


Tissue polypeptide antigen (TPA)

TPA is a protein marker that is found in high levels when there are many rapidly dividing cells in the body such as cancer cells. The TPA blood test is sometimes used along with tests for other tumor markers to help follow patients being treated for lung, bladder, and many other cancers. TPA levels are also elevated in some noncancerous conditions.


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