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Friday 6 April 2012

Tumor Markers

What are they?

Tumor markers are substances, usually proteins, that are produced by the body in response to cancer growth or by the cancer tissue itself and that may be detected in blood, urine, or tissue samples. Some tumor markers are specific for a particular type of cancer, while others are seen in several cancer types. Most of the well-known markers may also be elevated in non-cancerous conditions. Consequently, tumor markers alone are not diagnostic for cancer.

There are only a handful of well-established tumor markers that are routinely used by physicians. Many other potential markers are still being researched. Some markers cause great excitement when they are first discovered but, upon further investigation, prove to be no more useful than markers already in use.

The goal is to be able to screen for and diagnose cancer early, when it is the most treatable and before it has had a chance to grow and spread. So far, the only tumor marker to gain wide acceptance as a screening test is Prostate Specific Antigen (PSA) for prostate cancer in men. Even with PSA there is continued debate among experts and national organizations over the usefulness of this test for screening asymptomatic men. Other markers are either not specific enough (too many false positives, leading to expensive and unnecessary follow-up testing) or they are not elevated early enough in the disease process to be useful for screening.

Some people are at a higher risk for particular cancers because they have inherited a genetic mutation. While not considered tumor makers, there are tests that look for these mutations in order to estimate the risk of developing a particular type of cancer. BRCA1 and BRCA2 are examples of gene mutations related to an inherited risk of breast cancer and ovarian cancer. For more information, see our overview on genetic testing.


Why are they done?

Tumor markers are not diagnostic in themselves. A definitive diagnosis of cancer is made by looking at tissue biopsy specimens under a microscope. However, tumor markers provide information that can be used to:

  • Screen. Most markers are not suited for general screening, but some may be used in people with a strong family history of a particular cancer. As mentioned, PSA testing may be used to screen for prostate cancer.
  • Diagnose. In a person who has symptoms, tumor markers may be used to help identify the source of the cancer, such as CA-125 for ovarian cancer, and to help differentiate it from other conditions. Remember that tumor markers cannot diagnose cancer by themselves but aid in this process.
  • Stage. If a person does have cancer, tumor marker elevations can be used to help determine how far the cancer has spread into other tissues and organs.
  • Determine Prognosis. Some tumor markers can be used to help doctors determine how aggressive a cancer is likely to be.
  • Guide Treatment. A few tumor markers, such as Her2/neu, will give doctors information about what treatments their patients may respond to (for instance, breast cancer patients who are Her2/neu positive are more likely to respond to Herceptin treatment).
  • Monitor Treatment. Tumor markers can be used to monitor the effectiveness of treatment, especially in advanced cancers. If the marker level drops, the treatment is working; if it stays elevated, adjustments are needed. The information must be used with care, however, since other conditions can sometimes cause tumor markers to rise or fall.
  • Determine Recurrence. Currently, one of the most important uses for tumor markers is to monitor for cancer recurrence. If a tumor marker is elevated before treatment, low after treatment, and then begins to rise over time, then it is likely that the cancer is returning. (If it remains elevated after surgery, then chances are that not all of the cancer was removed.)  

Common Tumor Markers Currently in Use

Table of Markers
tumor markers cancers What else? When/how used Usual sample
AFP (Alpha-feto protein) Liver, germ cell cancer of ovaries or testes Also elevated during pregnancy Help diagnose, monitor treatment, and determine recurrence Blood
B2M (Beta-2 microglobulin) Multiple myeloma
and lymphomas
Present in many other conditions, including Crohn's disease and hepatitis; often used to determine cause of renal failure Determine prognosis Blood
CA 15-3 (Cancer antigen 15-3) Breast cancer and others, including lung, ovarian Also elevated in benign breast conditions; doctor can use CA 15-3 or CA 27.29 (two different assays for same marker) Stage disease, monitor treatment, and determine recurrence Blood
CA 19-9 (Cancer antigen 19-9) Pancreatic, sometimes colorectal and bile ducts Also elevated in pancreatitis and inflammatory bowel disease Stage disease, monitor treatment, and determine recurrence Blood
CA-125 (Cancer antigen 125) Ovarian Also elevated with endometriosis, some other benign diseases and conditions; not recommended as a general screen Help diagnose, monitor treatment, and determine recurrence Blood
Calcitonin Thyroid medullary carcinoma Also elevated in pernicious anemia and thyroiditis Help diagnose, monitor treatment, and determine recurrence Blood
CEA (Carcino-embryonic antigen) Colorectal, lung,
breast, thyroid, pancreatic, liver, cervix, and bladder
Elevated in other conditions such as hepatitis, COPD, colitis, pancreatitis, and in cigarette smokers Monitor treatment and determine recurrence Blood
Chromogranin A (CgA) Neuroendocrine tumors (carcinoid tumors, neuroblastoma) May be most sensitive tumor marker for carcinoid tumors To help diagnose and monitor Blood
Estrogen receptors Breast Increased in hormone-dependent cancer Determine prognosis and guide treatment Tissue
hCG (Human chorionic gonadotropin) Testicular and trophoblastic disease Elevated in pregnancy, testicular failure Help diagnose, monitor treatment, and determine recurrence Blood, urine
Her-2/neu Breast Oncogene that is present in multiple copies in 20-30% of invasive breast cancer Determine prognosis and guide treatment Tissue
Monoclonal immunoglobulins Multiple myeloma and Waldenstrom’s macroglobulinemia Overproduction of an immunoglobulin or antibody, usually detected by protein electrophoresis Help diagnose,
monitor treatment, and determine recurrence
Blood, urine
Progesterone receptors Breast Increased in hormone-dependent cancer Determine prognosis and guide treatment Tissue
PSA (Prostate specific antigen), total and free Prostate Elevated in benign prostatic hyperplasia, prostatitis and with age Screen for and help diagnose, monitor treatment, and determine recurrence Blood
Thyroglobulin Thyroid Used after thyroid is removed to evaluate treatment Determine recurrence Blood
Other Tumor Markers Less Widely Used
BTA (Bladder tumor antigen) Bladder Not widely available, but gaining acceptance Help diagnose and determine recurrence Urine
CA 72-4 (Cancer antigen 72-4) Ovarian No evidence that it is better than CA-125 but may be useful when combined with it; still being studied Help diagnose Blood
Des-gamma-carboxy prothrombin (DCP) Hepatocellular carcinoma (HCC) New test; often used along with an imaging study plus AFP and/or AFP-L3% to evaluate if someone with chronic liver disease has developed HCC To evaluate risk of developing HCC; to evaluate treatment; to monitor for recurrence Blood
EGFR (Her-1) Solid tumors, such as of the lung (non small cell), head and neck, colon, pancreas, or breast Not available in every laboratory Guide treatment and determine prognosis Tissue
NSE (Neuron-specific enolase) Neuroblastoma, small cell lung cancer May be better than CEA for following this particular kind of lung cancer Monitor treatment Blood
NMP22 Bladder Not widely used Help diagnose and determine recurrence Urine
Prostate-specific membrane antigen (PSMA) Prostate Not widely used; levels increase normally with age Help diagnose Blood
Prostatic acid phosphatase (PAP) Metastatic prostate cancer, myeloma, lung cancer Not widely used anymore; elevated in prostatitis and other conditions Help diagnose Blood
S-100 Metastatic melanoma Not widely used Help diagnose Blood
Soluble Mesothelin-Related Peptides (SMRP) Mesothelioma Often used in conjunction with imaging tests To monitor progression or recurrence Blood
TA-90 Metastatic melanoma Not widely used, being studied Help diagnose Blood

What are tumor markers?


Tumor markers are substances that can be found in the body when cancer is present. The classic tumor marker is a protein that can be found in the blood in at increased levels when a certain type of cancer is present, but not all tumor markers are like that. Some are found in urine or other body fluid, and others are found in tumors and other tissue. They can be products of the cancer cells themselves, or made by the body in response to cancer or other conditions. Most tumor markers are proteins, but some newer markers are genes or other substances.

There are many different tumor markers. Some are seen only in a single type of cancer, while others can be found in many types of cancer.

To test for a tumor marker, the doctor most often sends a sample of the patient's blood or urine to a lab. The marker is usually found by combining the blood or urine with man-made antibodies that react with the tumor marker protein. Sometimes a piece of the tumor itself is tested for tumor markers.

Tumor markers alone are rarely enough to show that cancer is present. Most tumor markers can be made by normal cells as well as by cancer cells. Sometimes, non-cancerous diseases can also cause levels of certain tumor markers to be higher than normal. And not every person with cancer may have higher levels of a tumor marker.

This is why only a few tumor markers are commonly used by most doctors. When a doctor looks at the level of a certain tumor marker, he or she will consider it along with the patient's history and physical exam and other lab tests or imaging tests.

In recent years, doctors have begun to develop newer types of tumor markers. With advances in technology, levels of certain genetic materials (DNA or RNA) can now be measured. It's been hard to identify single substances that provide useful information, but doctors are now beginning to look at patterns of genes or proteins in the blood. These new fields of genomics and proteomics are discussed in the section, "What's new in tumor marker research?"


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Source of the following article:
http://www.cancer.org/Treatment/UnderstandingYourDiagnosis/ExamsandTestDescriptions/TumorMarkers/tumor-markers-how-t-m-used

How are tumor markers used?


Tumor markers can be used in a number of ways.

Screening and early detection of cancer

Screening refers to looking for cancer in people who have no symptoms of the disease. Early detection is finding cancer at an early stage, when it is less likely to have spread and is easier to treat. Tumor markers were first developed to test for cancer in people without symptoms, but very few markers have been shown to be helpful in this way.

A perfect tumor marker could be used as a cancer screening blood test for all people. The tumor marker would only be found in people with cancer. It would tell doctors the type of cancer, how much cancer there is, and which treatment would work best. At this time there are no tumor marker tests that work like this.

Today, the most widely used tumor marker is the prostate-specific antigen (PSA) blood test. The PSA test is used to screen men for prostate cancer. People with prostate cancer usually have high PSA levels. But it's not always clear what the test results mean – high PSA levels can be seen in men without cancer, and a normal PSA does not always mean that no cancer is present. At this time, not all doctors agree that PSA screening is right for all men.

So far, no other tumor marker has been shown to help screen for cancer in the general population. A few of the markers that are now available can help find cancer at an early stage when only patients at high risk are tested.

Diagnosing cancer

Tumor markers are usually not used to diagnose cancer. In most cases, cancer can only be diagnosed by a biopsy (taking out some tumor cells so they can be looked at under a microscope). Still, markers can help figure out if a cancer is likely. And if a cancer is already widespread when it is found, tumor markers can help figure out where it started.

An example is a woman who has cancer throughout her pelvis and belly (abdomen). A high level of the tumor marker CA 125 will strongly suggest ovarian cancer, even if surgery can't find the source. This can be important because treatment can then be aimed at this type of cancer.

Alpha fetoprotein (AFP) is an example of a tumor marker that can be used to help diagnose cancer. This tumor marker can sometimes be used to help diagnose liver cancer. The level of AFP can go up with some liver diseases, but when it reaches a certain high level in someone with a liver tumor, doctors can be fairly sure that liver cancer is present (even without a biopsy).

Determining the outlook (prognosis) for certain cancers

Some types of cancer grow and spread faster than others. But even within a cancer type (such as testicular cancer), some cancers will grow and spread more quickly or may be more or less responsive to certain treatments. Sometimes the level of a tumor marker can help predict the behavior and outlook for certain cancers. For example, in testicular cancer, very high levels of a tumor marker like HCG or AFP predicts for a more aggressive cancer and a poorer outlook for survival. Patients with these high levels may be given more aggressive treatment to start.

Seeing if certain treatments are likely to work

Certain markers found on cancer cells can be used to help predict if a certain treatment is likely to work or not. For example, in breast and stomach cancer, if the cells have too much of a protein called HER2, drugs such as trastuzumab (Herceptin®) can be helpful in treatment. If the cancer cells have a normal amount of HER2, the drugs won't help, so tumor tissue is checked for HER2 before treatment is started.

Determining how well treatment is working

One of the most important uses for tumor markers is to watch patients being treated for cancer, especially advanced cancer. If a tumor marker is available for a certain type of cancer, the level of the marker may be able to be used to see if the treatment is working, instead of doing other tests like x-rays, CT scans, bone scans, or other tests.

If the tumor marker level in the blood goes down, it is almost always a sign that the treatment is working. On the other hand, if the marker level goes up, then the cancer is not responding and the treatment may need to be changed. (One exception is if the cancer is very sensitive to a certain chemotherapy treatment. In this case, the chemo can cause many cancer cells to die and release large amounts of the marker into the blood, which will cause the level of the tumor marker to rise for a short time.)

Detecting recurrent cancer

Tumor markers are also used to look for cancer that may have come back (recur) after treatment. Certain tumor markers may be useful once treatment is complete and there is no sign of cancer in the body. These include:
  • Prostate specific antigen (PSA) for prostate cancer
  • Human chorionic gonadotropin (HCG) for gestational trophoblastic tumors and some germ cell cancers
  • Alpha fetoprotein (AFP) for certain germ cell cancers and liver cancer
  • CA 125 for ovarian cancer
  • Carcinoembryonic antigen (CEA) for colon and rectal cancers
Some women who have been treated for breast cancer have blood tests for levels of the tumor marker CA 15-3. This can sometimes show that cancer has come back (recurred) before the woman has symptoms or the cancer can be seen on imaging tests. Many doctors question the test's value, though, because it isn't clear that it is better to treat recurrent breast cancer before it is causing symptoms. In studies done so far, starting treatment earlier has not helped women live longer or feel better.

Findings like this are why many experts do not recommend checking tumor markers after treatment aimed at curing most cancers. These markers are more likely to be used to keep an eye on advanced cancer during treatment.

When are tumor markers checked?

Whether or not tumor markers are followed depends on the type of cancer a person has. Tumor markers may be checked at the time of diagnosis; before, during, and after treatment; and then regularly for many years to see if the cancer has come back. During treatment, changes in tumor marker levels can be a sign of whether treatment is working.

Tumor marker levels can change over time. The changes are important, which is why a series of levels often has more meaning than a single result. If at all possible it is best to compare results from tests done at the same lab, and always be sure that the results are of the same value, such as ng/mL (nanograms per milliliter) or U/mL (units/milliliter).


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Source of the following article: http://www.cancer.org/Treatment/UnderstandingYourDiagnosis/ExamsandTestDescriptions/TumorMarkers/tumor-markers-drawbacks-of-t-m

The drawbacks of tumor markers


Early on in the search for tumor markers, the hope was that someday all cancers could be detected early with a blood test. A simple blood test that could find cancers in their earliest stages could prevent the deaths of millions of people. But very few tumor markers are useful for finding cancer at a very early stage. There are a few reasons for this:
  • Almost everyone has a small amount of these markers in their blood, so it is very hard to spot early cancers by using these tests.
  • The levels of these markers tend to get higher than normal only when there is a large amount of cancer present.
  • Some people with cancer never have higher levels of these markers.
  • Even when levels of these markers are high, it doesn't always mean that cancer is present. For example, the level of the tumor marker CA 125 can be high in women with gynecologic conditions other than ovarian cancer.
These reasons are why, today, tumor markers are used mainly in patients who have already been diagnosed with cancer to watch their response to treatment or look for the return of cancer after treatment.

Many other tumor markers have been found in recent years, and this remains an active area of cancer research. 
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Source of the following article: http://www.cancer.org/Treatment/UnderstandingYourDiagnosis/ExamsandTestDescriptions/TumorMarkers/tumor-markers-specific-markers

Specific tumor markers

This section focuses on some of the tumor markers often used today.

Tests for many other markers are available through commercial testing labs, but these are not commonly used. They may even be advertised as being better than the more common markers, but they haven't yet been shown to have an advantage over the others. In some cases like this, the tests have been taken off the market at the request of the Food and Drug Administration. Still, there are tests with unproven value available for many types of cancer.

There are also other markers that are used by researchers. These are often not available to doctors or hospital labs. If research does show that they are useful, they are then made available to doctors and their patients. The list below is limited to those tumor markers that are available to most doctors and have reliable scientific information showing that they are useful.

The cancers described in these brief summaries are those for which the marker is usually used. These marker levels may be increased in other kinds of cancer, too.

As with other kinds of lab tests, different labs may consider slightly different marker levels to be normal or abnormal. This can depend on a number of factors, including a person's age and gender, which test kit the lab uses, and how the test is done. The values listed below are average values, but most labs will list their own "reference ranges" along with any test results you get. If you are being tested for a tumor marker, be sure to ask your doctor about what your results mean.

Alpha-fetoprotein (AFP)

AFP can help diagnose and guide the treatment of liver cancer (hepatocellular carcinoma). Normal levels of AFP are usually less than 10 ng/mL (nanograms per milliliter). (A nanogram is one-billionth of a gram.) AFP levels are increased in most patients with liver cancer. AFP is also elevated in acute and chronic hepatitis, but it seldom gets above 100 ng/mL in these diseases.

In someone with a liver tumor, an AFP level over a certain value can mean 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 is also higher in certain germ cell tumors, such as some testicular cancers (those containing embryonal cell and endodermal sinus types), certain rare types of ovarian cancer (yolk sac tumor or mixed germ cell cancer), and germ cell tumors that start in the chest (mediastinal germ cell tumors). AFP is used to monitor the response to treatment, since high levels should go down with successful treatment. If the cancer has gone away with treatment the level should go back to normal. After that, any increase can be a sign that the cancer has come back.

Bcr-abl

In chronic myeloid leukemia (CML), the cancer (leukemia) cells contain a new, abnormal gene called bcr-abl. A test called PCR can find this gene in very small amounts in blood or bone marrow. In someone with blood and bone marrow findings consistent with CML, finding the gene confirms the diagnosis. Also, the level of the gene can be measured and used to guide treatment.

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

Beta-HCG

See human chorionic gonadotropin (HCG) below

Bladder tumor antigen (BTA)

BTA is found in the urine of many patients with bladder cancer. It may be a sign of some non-cancerous conditions, too, such as kidney stones or urinary tract infections. The results of the test are reported as either positive (BTA is present) or negative (BTA is not present). It is sometimes used along with NMP22 (see below) to test patients for the return (recurrence) of bladder cancer. This test is not often used but is gaining acceptance. It is not as good as cystoscopy (looking into the bladder through a thin, lighted tube) for finding bladder cancer, but it may be helpful in allowing cystoscopy to be done less often during bladder cancer follow-up. Most experts still consider cystoscopy the best way to diagnose and follow-up bladder cancer.

CA 15-3

CA 15-3 is mainly used to watch patients 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 if treatment is working, but they may go up in the first few weeks after treatment is started. This rise is caused when dying cancer cells spill their contents into the bloodstream.

The normal level is usually less than 30 U/mL (units/milliliter), depending on the lab. 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, like lung and ovarian, and in some non-cancerous conditions, like benign breast conditions and hepatitis.

CA 27.29

CA 27.29 is another marker that can be used to follow patients 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 it is a newer test than CA 15-3, it is not any better in detecting either early or advanced disease. It may be less likely to be positive in 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 other cancers and in some non-cancerous conditions, and 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 (the most common type of 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 the cancer is advanced. If the CA-125 level is increased at the time of diagnosis, changes in the CA 125 level can be used during treatment to get an idea of how well it's working.

Levels are also elevated in about half of women whose cancer has not spread outside of the ovary. This is why CA 125 has been studied as a screening test. The trouble with using it as a screening test is that it would still miss many early cancers, and problems other than ovarian cancer can cause an elevated CA 125 level. For example, it is often higher in women with uterine fibroids or endometriosis (having uterine cells in abnormal locations). It may also be higher in men and women with lung, pancreatic, breast, and colon cancer, and in people who have had cancer in the past. Because 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 in ovarian and pancreatic cancer and cancers starting 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 the level is often normal, so it is not good as a screening test. Still, it 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 also be used to watch colorectal cancer, but the CEA test is preferred for this type of 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, inflammatory bowel disease, and pancreatitis (inflammation of the pancreas).

Calcitonin

Calcitonin is a hormone produced by cells called parafollicular C cells in the thyroid gland. It normally helps regulate blood calcium levels. Normal calcitonin levels are below 5 to 12 pg/ml (picograms per milliliter). (A picogram is one trillionth of a gram.) In 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.

This is one of the rare tumor markers that can be used to help detect early cancer. Because MTC is often inherited, blood calcitonin can be measured to detect the cancer in its very earliest stages in family members known to be at risk. Other cancers, like lung cancers and leukemias, can also cause calcitonin levels to be elevated, but calcitonin blood levels are not usually used to follow these 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 outlook in patients with colorectal cancer. The normal range of blood levels varies from lab to lab, but levels higher than 3 ng/mL (nanograms per 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 follow patients with colorectal cancer during and after treatment. In this way CEA levels are used to see if the cancer is responding to treatment or to see if it has come back (recurred) after treatment.

CEA may be used for lung and breast cancer. This marker can be high in some other cancers, too like thyroid, pancreas, liver, stomach, prostate, ovary, cervix, and bladder cancer. If the CEA level is high at diagnosis, it can be used to follow the response to treatment. CEA can also be elevated in some non-cancerous diseases, like hepatitis, COPD, colitis, and pancreatitis, and in otherwise healthy smokers.

Chromogranin A

Chromogranin A (CgA) is made 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. It is probably the most sensitive tumor marker for carcinoid tumors. It is abnormal in 1 out of 3 people with localized disease and 2 out of 3 of those with cancer that has spread (metastatic cancer). Levels can also be elevated in some advanced forms of prostate cancer that have neuroendocrine features. The range of normal blood levels varies between testing centers, but is commonly less than 50 ng/mL (nanograms per milliliter).

Epidermal growth factor receptor (EGFR)

This protein, also known as HER1, is a receptor found on cells that helps them grow. Tests done on a piece of the cancer tissue can look for increased amounts of these receptors, which is a sign that the cancer may grow fast, spread, and be harder to treat. This means patients with elevated EGFR may have poorer outcomes and need more aggressive treatment, particularly with drugs that block (or inhibit) the EGFR receptors.

EGFR may be used to guide treatment and predict outcomes of non-small cell lung, head and neck, colon, pancreas, or breast cancers. The results are reported as a percentage based on the number of cells tested. This test is not yet widely available.

Some lung cancers have defects (mutations) in the EGFR gene that make it more likely that certain drugs will work against the cancer. These gene changes are more common in lung cancer patients who are women, non-smokers, or Asian.

Hormone receptors

Breast tumor samples – not blood samples – from all cases of breast cancer are tested for estrogen and progesterone receptors. These 2 hormones often fuel the growth of breast cancer cells. 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. Hormone receptor-positive breast 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 tells some cancer cells to grow. It is elevated in about 1 out of 5 breast cancers. Higher than normal levels can be found in some other cancers, too, such as some stomach cancers. The HER2 level is usually found by testing a sample of the cancer tissue itself, not the blood. Cancers that are HER2-positive tend to grow and spread faster than other cancers.

All newly diagnosed breast cancers and advanced stomach cancers should be tested for HER2. HER2-positive cancers are more likely to respond to treatments which work against the HER2 receptor on 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) and in gestational trophoblastic disease, mainly choriocarcinoma. They are also higher in some people with mediastinal germ cell tumors – cancers in the middle of the chest (the mediastinum) 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 and can be followed over time to see how well treatment is working. They can also be used to look for cancer that has come back after treatment has ended (recurrence).

An elevated blood level of HCG will also raise suspicions of cancer in certain situations. For example, in a woman who still has a large uterus after pregnancy has ended, a high blood level of this marker may be a sign of a cancer. This is also true of men with an enlarged testicle or anyone with a tumor in their chest.

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.

Immunoglobulins

Immunoglobulins are not classic tumor markers but instead are antibodies, which are 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.

There are normally many different immunoglobulins in the blood, with each one differing very slightly from the others. A classic sign in patients with myeloma or macroglobulinemia is a very high level of a certain monoclonal immunoglobulin. This can be seen on a test called serum protein electrophoresis (also called SPEP). In this test, the blood proteins are separated by an electrical current. With 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 because 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 followed over time to help see how well treatment is working.

Free light chains

Immunoglobulins are made up of protein chains: 2 long (heavy) chains and 2 shorter (light) chains. Sometimes in multiple myeloma an M protein can't be found but the level of the light chain part the blood is high, instead. This level can be measured with a test called free light chains, and be used to help guide treatment.

KRAS

Cetuximab (Erbitux®) and panitumumab (Vectibix®) are drugs targeting the EGFR protein that can be useful in the treatment of advanced colorectal cancer. These drugs don't work in colorectal cancers that have mutations (defects) in the K-ras gene. Doctors now commonly test the tumor for this gene change and only use these drugs in people whose cancers do not have the mutation.
K-ras mutations can also help guide treatment for some types of lung cancer. Tumors with the mutations do not respond to treatment with erlotinib (Tarceva®) or gefitinib (Iressa®).

Lactate dehydrogenase (LDH)

LDH is used as a tumor marker for testicular cancer and other germ cell tumors. It is not as useful as AFP and HCG for diagnosis because its level can be up with many other things besides cancer, including blood and liver problems. Still, high levels of LDH predict a poorer outlook for survival. LDH levels are also used to monitor the effect of treatment and to watch for recurrent disease.

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 per milliliter).

NMP22

NMP22 is a protein found in the nucleus (control center) of cells. Levels of NMP22 are often elevated (more than 10 U/mL or units/milliliter) in the urine of people with bladder cancer. This test is not widely used at this time. So far it hasn't been found to be sensitive enough to be used as a screening tool. It is most often used to look for bladder cancer that has come back after treatment. This is a less invasive way to look for cancer than cystoscopy (looking into the bladder with a thin, lighted tube), but it's not always as accurate. NMP22 testing can't take the place of cystoscopy completely, but it may allow doctors to do this procedure less often. NMP22 levels can also be higher than normal with some non-cancerous conditions or due to recent chemo treatment.

Prostate-specific antigen (PSA)

PSA is a tumor marker for prostate cancer. It is the only marker used to screen for a common type of cancer, but most medical groups do not recommend using it routinely to screen all men (instead recommending that men make informed decisions for themselves about testing). PSA is a protein made by cells of the prostate gland, which is found only in men. The prostate gland makes some of the liquid in semen.

The level of PSA in the blood can be elevated in prostate cancer, but PSA levels can be affected by other things, too. 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 2 after ejaculation.

PSA is measured in nanograms per milliliter (ng/mL). Most doctors feel that a blood PSA level below 4 ng/mL means cancer is unlikely. Levels greater than 10 ng/mL mean cancer is likely. The area between 4 and 10 is a gray zone. Men with PSA levels in this borderline range have about a 1 in 4 chance of having prostate cancer. A doctor may recommend a prostate biopsy (getting samples of prostate tissue to look for cancer) for a man with a PSA level above 4 ng/mL.

Not all doctors agree with these cutoff points. This is because some men with prostate cancer do not have an elevated PSA level, while some others with a borderline or elevated level will not have cancer.

Some doctors believe it is more useful to follow the PSA level over time because an increase from one year to the next may mean prostate cancer is more likely. This is called PSA velocity. Most doctors believe that PSA levels should be measured at least 3 times over a period of at least 18 months in order to get an accurate PSA velocity. Even then, it's not clear if measuring PSA velocity is any more helpful than looking at PSA levels alone.

Doctors are also looking at the PSA level in other ways to see if it might be more useful.

A helpful test 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 2 forms – some is bound to a protein and some is free. 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 a biopsy should be done. (Higher total PSA levels with lower free PSA levels are linked to a higher chance of having prostate cancer.)

The PSA test is very valuable in monitoring the response to treatment and 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 go down after treatment (although it doesn't go away completely). A rise in the PSA level may be a sign the cancer is coming back.

Prostatic acid phosphatase (PAP)

PAP (not to be confused with the Pap test for women) is another test for prostate cancer. It was used before the PSA test was developed but is seldom used now because the PSA test is better. It may also be used to help diagnose multiple myeloma and lung cancer.

Prostate-specific membrane antigen (PSMA)

PSMA is a substance found in all prostate cells. Blood levels increase with age and with prostate cancer. PSMA is a very sensitive marker, but so far it has not proven to be better than PSA. Its use in finding or following cancer is still being studied. Its current use is limited to being part of a nuclear scan (a type of imaging test) to look for the spread of prostate cancer in the body. Some potential immunotherapy treatments for prostate cancer based on PSMA are now under study.

S-100

S-100 is a protein found in most melanoma cells. Tissue samples of suspected melanomas may be tested for this marker to help in diagnosis.

Some studies have shown that blood levels of S-100 are elevated in most patients with metastatic melanoma. The test is sometimes used to look for melanoma spread before, during, or after treatment.

TA-90

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

Thyroglobulin

Thyroglobulin is a protein made by the thyroid gland. Normal blood levels depend on a person's age and gender. Thyroglobulin levels are elevated in many thyroid diseases, including some common forms of thyroid cancer.

Treatment for thyroid cancer often involves removing the entire thyroid gland, sometimes along with radiation therapy. Thyroglobulin levels in the blood should fall to undetectable levels after treatment. A rise in the thyroglobulin level after treatment may mean the cancer has come back. In people with thyroid cancer that has spread, thyroglobulin levels can be followed over time to evaluate the results of treatment.

Some people's immune systems make antibodies against thyroglobulin, which can affect test results. This is why levels of anti-thyroglobulin antibodies are often measured at the same time. 

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Source of the following article: http://www.cancer.org/Treatment/UnderstandingYourDiagnosis/ExamsandTestDescriptions/TumorMarkers/tumor-markers-common-ca-and-t-m

Common cancers and the tumor markers linked to them


This list covers more common cancers and the tumor markers that are most often linked to them. It is in no way a complete list. Your doctor may check other tumor markers, too. Be sure to ask your doctor if you are not sure which markers are being checked, what they may tell you about the cancer, and what the levels mean in your case. More specific information on the tumor markers is covered above.

Bladder cancer

No tumor markers in urine are recommended for bladder cancer screening.

The bladder tumor antigen (BTA) and the NMP22 tests can be used along with cystoscopy (using a thin, lighted tube to look in the bladder) in diagnosing it in patients with symptoms. These tests are also being used to follow some patients after treatment, though cystoscopy and urine cytology (using a microscope to look for cancer cells in the urine) are still recommended as the standard tests for diagnosis and follow-up. BTA and NMP22 tests are often used between cystoscopies. Normal values may allow cystoscopy to be done less often. These tests do not take the place of urine cytology and cystoscopy.

For advanced bladder cancer, some of the markers used for other cancers such as CEA, CA 125, CA 19-9, and TPA may be elevated and can be used to follow patients during and after treatment.
For more information see our document called Bladder Cancer.

Breast cancer

No tumor marker has been found to be useful for screening or diagnosing early stage breast cancer.
At the time of diagnosis, breast cancer tissue should be tested for hormone receptors (estrogen and progesterone), as well as the HER2/neu antigen. These markers give information on how likely the cancer is to grow fast and spread and how likely it is to respond to certain treatments.

The markers most often used to follow patients with advanced cancer or to look for the return (recurrence) of the cancer after treatment are CA 15-3 and CEA. The CA 27.29 test is also used by some doctors. The CA 15-3 and CA 27.29 are probably equally sensitive, while the CEA is less sensitive.

These markers are most useful in measuring the results of treatment for patients with advanced disease. In most cases, blood levels go down if the cancer responds to treatment and rise if the cancer progresses.

Some doctors use these tests to look for signs of recurrence in women who have no symptoms of cancer after their first treatment. But most professional groups do not recommend using these markers to follow women already treated for early stage disease.

For more information see our document called Breast Cancer.

Chronic myeloid leukemia

Chronic myeloid leukemia (CML), also known as chronic myelogenous leukemia, is a type of cancer that starts in the blood-forming cells of the bone marrow and invades the blood. In CML, leukemia cells tend to build up in the body over time, but in many cases people don't have any symptoms for at least a few years. The leukemia cells in CML contain an abnormal gene, bcr-abl. This gene can be found in the blood and bone marrow of patients with this disease, even when it is only present in tiny amounts. A test for this gene can confirm the diagnosis of CML in a patient who is suspected of having the disease. It is also useful in guiding treatment. If treatment is working, the level of this gene should go down. A rise in the level may mean that the current treatment is no longer working, and a new treatment should be started.

For more information, see our document called Leukemia - Chronic Myeloid (Myelogenous).

Colorectal cancer

The markers most often elevated in advanced colorectal cancer are CEA and CA 19-9, but neither of these is useful as a screening test for colorectal cancer.

An elevated CEA before surgery may be a sign of a poorer outcome. If it is high before surgery, the CEA should go to normal levels in about 4 to 6 weeks if all of the cancer has been removed. Many doctors follow patients after surgery with CEA tests every 3 to 6 months or so to look for the return of the cancer (recurrence).

CEA is also used to follow patients who are being treated for advanced or recurrent disease. The CEA level will go down if the treatment is working and will rise if the cancer progresses.

If the CEA is not elevated in patients with advanced or recurrent cancer, sometimes the CA 19-9 can be used to follow the disease.

If treatment with drugs that target EGFR, such as cetuximab (Erbitux) or panitumumab (Vectibix) is considered, the cancer tissue will first be tested to see if the cells contain K-ras mutations. If a mutation is present, these drugs are not likely to work, and so will not be given.

For more information see our document called Colorectal Cancer.

Gestational trophoblastic disease

Trophoblastic tumors include molar pregnancies (a pregnancy that results in a tumor of the placenta) and choriocarcinoma. Human chorionic gonadotropin (HCG) is elevated in these tumors. HCG testing can be used to find these cancers in women who are no longer pregnant but still have an enlarged uterus.

HCG measurements during treatment for trophoblastic disease are very useful in looking at response to treatment. After treatment, HCG levels should return to normal. Any further increase could be a sign that the cancer has come back.

For more information see our document called Gestational Trophoblastic Disease.

Liver cancer

Liver cancers can cause elevated levels of alpha fetoprotein (AFP). Higher AFP levels occur in most patients with liver cancer. An elevated AFP in someone with chronic hepatitis or cirrhosis may suggest that they have this cancer and lead to testing to see if the liver contains a tumor.

Liver cancer is not very common in the United States, so AFP testing is not used to test the general population for this type of cancer. Screening with AFP has been successful in parts of Asia where liver cancer is common. Sometimes the cancer is found early enough so that the patient can be cured with surgery. Because of this success, some doctors in the United States may screen their patients who have cirrhosis of the liver or hepatitis B or C. A rising AFP level might be a sign of cancer.

AFP can also be used to help figure out the best treatment for liver cancer and to follow patients after curative surgery or other treatment.

For more information see our document called Liver Cancer.

Lung cancer

No tumor markers have proven useful as screening tests for lung cancer.

Some of the tumor markers that may be elevated in lung cancer are the carcinoembryonic antigen (CEA) in non-small cell lung cancer and the neuron-specific enolase (NSE) in small cell lung cancer. Sometimes doctors will follow these markers to evaluate treatment results. There are many other markers that can also be followed. But because lung cancer is fairly easily seen on chest x-rays or other imaging tests, tumor markers play a less important role.

Cancer tissue may be tested for defects in the epidermal growth factor receptor (EGFR) to see if the drugs erlotinib (Tarceva®) or gefitinib (Iressa®) may be helpful.

For more information see our documents called Lung Cancer (Non-Small Cell) or Lung Cancer (Small Cell).

Melanoma skin cancer

No tumor marker is of value in finding this disease early.

The markers TA-90, S-100, and some other markers can be used to test tissue samples to help see if a tumor is melanoma.

Blood levels of TA-90 have also been used to help find out if the melanoma has spread (metastasized). If the blood TA-90 level is high, there is a good chance the melanoma has spread beyond where it first started. But TA-90 can sometimes be high even if the melanoma hasn’t metastasized. This is why it has not yet been used to plan treatment or predict outlook.

S-100 is also elevated in the blood when the disease is widespread. This marker can also be used to see if the melanoma has progressed.

For more information see our document called Melanoma Skin Cancer.

Multiple myeloma

There are no classic tumor markers commonly used to screen for this disease, but tests for immunoglobulins or free light chains can be used to help detect it or make a diagnosis. These immune system proteins can be found in the blood or urine of most patients with myeloma.

Pieces of immunoglobulins in the urine, called Bence Jones proteins, are found in some patients with multiple myeloma. Most people with myeloma also have detectable levels of a certain immunoglobulin, called a monoclonal protein or M-protein, in their blood. This protein leads to a monoclonal spike, or M spike, on a protein electrophoresis. These proteins can help diagnose the disease, but a bone marrow biopsy may be needed to confirm the diagnosis. Many of the people with myeloma who do not have an M spike instead have elevated levels of free light chains (a light chain is a piece of the immunoglobulin molecule). These markers are also helpful in tracking the course of the disease and its response to treatment.

Many patients with multiple myeloma also have higher blood levels of beta-2-microglobulin, which can also give information on outlook and the response to treatment.

For more information see our document called Multiple Myeloma.

Ovarian cancer

Epithelial ovarian cancer (the most common form of ovarian cancer) is linked with elevated levels of CA 125. Other markers that are sometimes measured are CA 72-4, CEA, and LASA-P. CA 125 is elevated in most women with advanced disease, and is the standard marker that most doctors use.
Ovarian cancer, even when advanced, is often confined to the abdomen (belly) and pelvis and hard to find through x-ray testing. This is why the CA 125 is often the easiest and best way to measure the response to treatment or to find a cancer that has come back.

CA 125 has been studied as a screening tool. At the present time, most medical groups do not recommend CA 125 testing for ovarian cancer screening in women who are not at increased risk because it doesn't seem to find the cancer early enough to help women live longer. Another problem with this test is that ovarian cancer is not common, and the CA 125 level can be elevated in other cancers and other conditions. So an elevated CA 125 is more likely to be due to some other cause, and more tests, including surgery, are often needed to rule out ovarian cancer.

CA 125 is used by some doctors to screen for ovarian cancer in women at increased risk because of a strong family history of ovarian cancers. These women usually get regular ultrasounds for early detection along with CA 125 tests. Still, even in women with a high risk of ovarian cancer, this testing has not yet been found to find the cancers early or help women live longer.

The second most common group of ovarian cancers is the germ cell tumors. Patients with these cancers often have elevated levels of HCG and/or AFP, which are useful in diagnosis and follow-up.

For more information see our document called Ovarian Cancer.

Pancreatic cancer

No markers have been found to be helpful in screening for pancreatic cancer.

The CA 19-9 marker is the most useful marker for pancreatic cancer. Most people with pancreatic cancer have elevated levels of CA 19-9 in their blood. The higher the level, the more likely the disease has spread. CA 19-9 levels give information about the outlook for people with pancreatic cancer but cannot be used to diagnose the disease.

CA 19-9 levels can be useful in patient follow-up. Patients whose levels drop to normal after surgery have a much better outlook than those people whose CA 19-9 remains high after surgery. This marker can also be used to follow the effects of treatment on more advanced disease and to watch for cancer that has come back after treatment.

Some doctors also follow the level of CEA in the blood, but it may not be as helpful as the CA 19-9 level.

For more information see our document called Pancreatic Cancer.

Prostate cancer

The marker most often used to detect prostate cancer is the prostate-specific antigen (PSA). Prostate cancer can often be found in its early stages by measuring blood levels of PSA. Still, most medical groups recommend that men decide for themselves whether getting screened with the PSA test is right for them.

PSA is very useful in finding cancer that has come back after treatment (recurrent disease). After surgery, the PSA level should be undetectable or near undetectable (0 or very close to 0). Those treated with radiation therapy should also have a huge drop in PSA after treatment, but it can take years before it goes back to normal. (It does not drop to undetectable levels after radiation therapy because some prostate cells stay in the body.) A rise in PSA after treatment could mean the disease is coming back and that more treatment should be considered. The PSA can also be used to follow the response to treatment for more advanced disease.

Another marker being studied for following prostate cancer is the prostate-specific membrane antigen (PSMA). It's not yet clear how useful it will be.

A rare type of prostate cancer, small cell, has neuroendocrine features. It often does not cause abnormal blood PSA levels or respond well to hormone therapy. Men with these cancers may have higher than normal levels of chromogranin A. These cancers are more likely to respond to certain chemotherapy drugs.

Prostatic acid phosphatase (PAP) is an older, less sensitive marker which is no longer used very much.

For more information see our document called Prostate Cancer.

Stomach (gastric) cancer

No marker has been developed for this cancer. Some other digestive cancer markers may be elevated, such as CEA, CA 72-4, and/or CA 19-9. If the levels of these markers are elevated at the time of diagnosis, the levels can be followed while the cancer is being treated.

For stomach cancers that have spread, tumor tissue will be tested for HER2 to see if certain drugs will be helpful as a part of treatment.

For more information see our document called Stomach Cancer.

Testicular cancer

Tumor markers are very important in this cancer and are used by doctors to follow its course. Human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) are usually elevated in the blood of men with testicular cancer. Lactate dehydrogenase (LDH) is another marker that is sometimes used, but is less helpful than these others. There are different kinds of testicular cancers, and they differ in the level and kind of marker that is elevated.

Seminoma

About 10% of men with seminoma, a type of testicular cancer, will have elevated HCG. Some will have elevated LDH, but none will have elevated AFP.

Non-seminoma

More than half of men with early stage disease will have elevated HCG or AFP or both. Many will also have high levels of LDH. These markers are elevated in most men with advanced disease. The amount of the marker found in the blood at the time of diagnosis does not often help in predicting outcome, but very high levels of these markers can be a sign of a poorer outlook.

HCG is almost always elevated and AFP is never elevated in choriocarcinoma, a subtype of non-seminoma. In contrast AFP, but not HCG, is elevated in another subtype known as yolk sac tumor or endodermal sinus tumor. Many tumors are made up of a mixture of different types of non-seminoma.

For more information see our document called Testicular Cancer.


Last Medical Review: 03/24/2011
Last Revised: 03/24/2011