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.
Beta-HCG
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
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.
Immunoglobulins
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
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
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.
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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
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
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.
