Tumor Markers
https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet
On This Page
1. What are tumor markers?
2. How are tumor markers used in cancer care?
3. How are tumor markers measured?
4. Does NCI have guidelines for the use of tumor markers?
5. What tumor markers are currently being used, and for which cancer types?
6. Can tumor markers be used in cancer screening?
7. What kind of research is under way to develop more accurate tumor markers?
8- Selected references
1. What are tumor markers?
Tumor markers are substances that are produced by cancer or by other cells of the
body in response to cancer or certain benign (noncancerous) conditions.
Most tumor markers are made by normal cells as well as by cancer cells; however,
they are produced at much higher levels in cancerous conditions. These substances
can be found in the blood, urine, stool, tumor tissue, or other tissues or bodily
fluids of some patients with cancer. Most tumor markers are proteins. However,
more recently, patterns of gene expression and changes to DNA have also begun to be used
as tumor markers.
Many different tumor markers have been characterized and are in clinical use. Some are
associated with only one type of cancer, whereas others are associated with two or more
cancer
types. No “universal” tumor marker that can detect any type of cancer has been found.
There are some limitations to the use of tumor markers. Sometimes, noncancerous conditions
can cause the levels of certain tumor markers to increase. In addition, not everyone with
a particular type of cancer will have a higher level of a tumor marker associated with
that cancer.
Moreover, tumor markers have not been identified for every type of cancer.
2. How are tumor markers used in cancer care?
Tumor markers are used to help detect, diagnose, and manage some types of cancer.
Although an elevated level of a tumor marker may suggest the presence of cancer,
this alone is not enough to diagnose cancer. Therefore, measurements of tumor markers
are usually combined with other tests, such as biopsies, to diagnose cancer.
Tumor marker levels may be measured before treatment to help doctors plan the appropriate
therapy. In some types of cancer, the level of a tumor marker reflects the stage (extent)
of the disease and/or the patient’s prognosis (likely outcome or course of disease). More
information about cancer staging is available on the Staging page.
Tumor markers may also be measured periodically during cancer therapy. A decrease in the
level of a tumor marker or a return to the marker’s normal level may indicate that the
cancer is responding to treatment, whereas no change or an increase may indicate that the
cancer is not responding.
Tumor markers may also be measured after treatment has ended to check for recurrence
(the return of cancer).
3. How are tumor markers measured?
A doctor takes a sample of tumor tissue or bodily fluid and sends it to a laboratory,
where various methods are used to measure the level of the tumor marker.
If the tumor marker is being used to determine whether treatment is working or whether
there is a recurrence, the marker’s level will be measured in multiple samples taken over
time. Usually these “serial measurements,” which show whether the level of a marker is
increasing, staying the same, or decreasing, are more meaningful than a single measurement.
4. Does NCI have guidelines for the use of tumor markers?
NCI does not have such guidelines. However, some national and international organizations
do have guidelines for the use of tumor markers for some types of cancer:
The American Society of Clinical Oncology (ASCO) has published clinical practice
guidelinesExit Disclaimer on a variety of topics, including tumor markers for breast cancer,
colorectal cancer, lung cancer, and others.
The National Academy of Clinical Biochemistry publishes laboratory medicine practice
guidelines, including Use of Tumor Markers in Clinical Practice: Quality Requirements
Exit Disclaimer, which focuses on the appropriate use of tumor markers for specific cancers.
5. What tumor markers are currently being used, and for which cancer types?
A number of tumor markers are currently being used for a wide range of cancer types. Although most of these can be tested in laboratories that meet standards set by the Clinical Laboratory Improvement Amendments, some cannot be and may therefore be considered experimental. Tumor markers that are currently in common use are listed below.
ALK gene rearrangements and overexpression
Cancer types: Non-small cell lung cancer and anaplastic large cell lymphoma
Tissue analyzed: Tumor
How used: To help determine treatment and prognosis
Alpha-fetoprotein (AFP)
Cancer types: Liver cancer and germ cell tumors
Tissue analyzed: Blood
How used: To help diagnose liver cancer and follow response to treatment;
to assess stage, prognosis, and response to treatment of germ cell tumors
Beta-2-microglobulin (B2M)
Cancer types: Multiple myeloma, chronic lymphocytic leukemia, and some lymphomas
Tissue analyzed: Blood, urine, or cerebrospinal fluid
How used: To determine prognosis and follow response to treatment
Beta-human chorionic gonadotropin (Beta-hCG)
Cancer types: Choriocarcinoma and germ cell tumors
Tissue analyzed: Urine or blood
How used: To assess stage, prognosis, and response to treatment
BRCA1 and BRCA2 gene mutations
Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To determine whether treatment with a particular type of targeted therapy is appropriate
BCR-ABL fusion gene (Philadelphia chromosome)
Cancer type: Chronic myeloid leukemia, acute lymphoblastic leukemia, and acute myelogenous leukemia
Tissue analyzed: Blood and/or bone marrow
How used: To confirm diagnosis, predict response to targeted therapy, and monitor disease status
BRAF V600 mutations
Cancer types: Cutaneous melanoma and colorectal cancer
Tissue analyzed: Tumor
How used: To select patients who are most likely to benefit from treatment with certain targeted therapies
C-kit/CD117
Cancer types: Gastrointestinal stromal tumor and mucosal melanoma
Tissue analyzed: Tumor
How used: To help in diagnosing and determining treatment
CA15-3/CA27.29
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6059737/figure/f1-or-40-01-0145/
Cancer type: Breast cancer
Tissue analyzed: Blood
How used: To assess whether treatment is working or disease has recurred
CA19-9
Cancer types: Pancreatic cancer, gallbladder cancer, bile duct cancer, and
gastric cancer
Tissue analyzed: Blood
How used: To assess whether treatment is working
CA-125
Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To help in diagnosis, assessment of response to treatment, and evaluation of recurrence
Calcitonin
Cancer type: Medullary thyroid cancer
Tissue analyzed: Blood
How used: To aid in diagnosis, check whether treatment is working, and assess recurrence
Carcinoembryonic antigen (CEA)
Cancer types: Colorectal cancer and some other cancers
Tissue analyzed: Blood
How used: To keep track of how well cancer treatments are working or check if cancer has come back
CD20
Cancer type: Non-Hodgkin lymphoma
Tissue analyzed: Blood
How used: To determine whether treatment with a targeted therapy is appropriate
Chromogranin A (CgA)
Cancer type: Neuroendocrine tumors
Tissue analyzed: Blood
How used: To help in diagnosis, assessment of treatment response, and evaluation of recurrence
Chromosomes 3, 7, 17, and 9p21
Cancer type: Bladder cancer
Tissue analyzed: Urine
How used: To help in monitoring for tumor recurrence
Circulating tumor cells of epithelial origin (CELLSEARCH®)
Cancer types: Metastatic breast, prostate, and colorectal cancers
Tissue analyzed: Blood
How used: To inform clinical decision making, and to assess prognosis
Cytokeratin fragment 21-1
Cancer type: Lung cancer
Tissue analyzed: Blood
How used: To help in monitoring for recurrence
EGFR gene mutation analysis
Cancer type: Non-small cell lung cancer
Tissue analyzed: Tumor
How used: To help determine treatment and prognosis
Estrogen receptor (ER)/progesterone receptor (PR)
Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To determine whether treatment with hormone therapy and some targeted therapies is appropriate
Fibrin/fibrinogen
Cancer type: Bladder cancer
Tissue analyzed: Urine
How used: To monitor progression and response to treatment
HE4
Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To plan cancer treatment, assess disease progression, and monitor for recurrence
HER2/neu gene amplification or protein overexpression
Cancer types: Breast cancer, gastric cancer, and gastroesophageal junction adenocarcinoma
Tissue analyzed: Tumor
How used: To determine whether treatment with certain targeted therapies is appropriate
Immunoglobulins
Cancer types: Multiple myeloma and Waldenström macroglobulinemia
Tissue analyzed: Blood and urine
How used: To help diagnose disease, assess response to treatment, and look for recurrence
KRAS gene mutation analysis
Cancer types: Colorectal cancer and non-small cell lung cancer
Tissue analyzed: Tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate
Lactate dehydrogenase
Cancer types: Germ cell tumors, lymphoma, leukemia, melanoma, and neuroblastoma
Tissue analyzed: Blood
How used: To assess stage, prognosis, and response to treatment
Neuron-specific enolase (NSE)
Cancer types: Small cell lung cancer and neuroblastoma
Tissue analyzed: Blood
How used: To help in diagnosis and to assess response to treatment
Nuclear matrix protein 22
Cancer type: Bladder cancer
Tissue analyzed: Urine
How used: To monitor response to treatment
Programmed death ligand 1 (PD-L1)
Cancer type: Non-small cell lung cancer
Tissue analyzed: Tumor
How used: To determine whether treatment with a particular type of targeted therapy is appropriate
Prostate-specific antigen (PSA)
Cancer type: Prostate cancer
Tissue analyzed: Blood
How used: To help in diagnosis, assess response to treatment, and look for recurrence
Thyroglobulin
Cancer type: Thyroid cancer
Tissue analyzed: Blood
How used: To evaluate response to treatment and look for recurrence
Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor (PAI-1)
Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To determine aggressiveness of cancer and guide treatment
5-Protein signature (OVA1®)
Cancer type: Ovarian cancer
Tissue analyzed: Blood
How used: To pre-operatively assess pelvic mass for suspected ovarian cancer
21-Gene signature (Oncotype DX®)
Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To evaluate risk of recurrence
70-Gene signature (Mammaprint®)
Cancer type: Breast cancer
Tissue analyzed: Tumor
How used: To evaluate risk of recurrence
6. Can tumor markers be used in cancer screening?
Because tumor markers can be used to assess the response of a tumor to treatment and for prognosis, researchers have hoped that they might also be useful in screening tests that aim to detect cancer early, before there are any symptoms. For a screening test to be useful, it should have very high sensitivity (ability to correctly identify people who have the disease) and specificity (ability to correctly identify people who do not have the disease). If a test is highly sensitive, it will identify most people with the disease—that is, it will result in very few false-negative results. If a test is highly specific, only a small number of people will test positive for the disease who do not have it—in other words, it will result in very few false-positive results.
Although tumor markers are extremely useful in determining whether a tumor is responding to treatment or assessing whether it has recurred, no tumor marker identified to date is sufficiently sensitive or specific to be used on its own to screen for cancer.
For example, the prostate-specific antigen (PSA) test, which measures the level of PSA in the blood, is often used to screen men for prostate cancer. However, an increased PSA level can be caused by benign prostate conditions as well as by prostate cancer, and most men with an elevated PSA level do not have prostate cancer. Initial results from two large randomized controlled trials, the NCI-sponsored Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO), and the European Randomized Study of Screening for Prostate Cancer,
showed that PSA testing at best leads to only a small reduction in the number of prostate cancer deaths. Moreover, it is not clear whether the benefits of PSA screening outweigh the harms of follow-up diagnostic tests and treatments for cancers that in many cases would never have threatened a man’s life.
Similarly, results from the PLCO trial showed that CA-125, a tumor marker that is sometimes elevated in the blood of women with ovarian cancer but can also be elevated in women with benign conditions, is not sufficiently sensitive or specific to be used together with transvaginal ultrasound to screen for ovarian cancer in women at average risk of the disease. An analysis of 28 potential markers for ovarian cancer in blood from women who later went on to develop ovarian cancer found that none of these markers performed even as well as CA-125 at detecting the disease in women at average risk.
7. What kind of research is under way to develop more accurate tumor markers?
Cancer researchers are turning to proteomics (the study of protein structure, function, and patterns of expression) in hopes of developing new biomarkers that can be used to identify disease in its early stages, to predict the effectiveness of treatment, or to predict the chance of cancer recurrence after treatment has ended.
Scientists are also evaluating patterns of gene expression for their ability to help
determine a patient’s prognosis or response to therapy. For example, results of the NCI-sponsored Trial Assigning IndividuaLized Options for Treatment (Rx), or TAILORx , showed that for women recently diagnosed with lymph node–negative, hormone receptor–positive, HER2-negative breast cancer who had undergone surgery, those with the lowest 21-gene (Oncotype Dx®) recurrence scores had very low recurrence rates when given hormone
therapy alone and thus can be spared chemotherapy. The trial is ongoing to see
whether women at intermediate risk of recurrence, based on the 21-gene test,
do better with chemotherapy in addition to hormone therapy than with hormone therapy alone.
More information on NCI’s role in supporting research on novel tools and methods for diagnosing cancer is available on the Diagnosis research page.
8. Selected References
Bigbee W, Herberman RB. Tumor markers and immunodiagnosis. In: Bast RC Jr., Kufe DW, Pollock RE, et al., editors. Cancer Medicine. 6th ed. Hamilton, Ontario, Canada: BC Decker Inc., 2003.
Andriole G, Crawford E, Grubb R, et al. Mortality results from a randomized
rostate-cancer screening trial. New England Journal of Medicine 2009; 360(13):1310–1319.
[PubMed Abstract]
Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. New England Journal of Medicine 2009; 360(13):1320–1328.
[PubMed Abstract]
Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled
Trial. JAMA 2011; 305(22):2295–2303. [PubMed Abstract]
Cramer DW, Bast RC Jr, Berg CD, et al. Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prevention Research
2011; 4(3):365–374. [PubMed Abstract]
Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. New England Journal of Medicine 2015; First published online September
28, 2015. doi: 10.1056/NEJMoa1510764Exit Disclaimer.
Related Resources
Prostate-Specific Antigen (PSA) Test
Targeted Cancer Therapies
Understanding Cancer Prognosis
Understanding Laboratory Tests
Reviewed: November 4, 2015
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