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What are tumor markers?
Tumor markers are substances, often proteins, that are produced by the cancer tissue itself or sometimes by the body in response to cancer growth. Because some of these substances can be detected in body samples such as blood, urine, and tissue, these markers may be used, along with other tests and procedures, to help detect and diagnose some types of cancer, predict and monitor a person’s response to certain treatments, and detect recurrence.
More recently, the idea of what constitutes a tumor marker has broadened. Newer types of tests have been developed that look for changes in genetic material (DNA, RNA), rather than proteins, in patient samples. The genetic changes have been found to be associated with certain cancers and can be used as tumor markers to help determine prognosis, guide targeted treatment, and/or detect cancers early on. Moreover, advances in technology have led to tests that can evaluate several genetic markers or panels of markers at the same time, providing expanded information about characteristics of a tumor. Examples of these are included, along with more traditional tumor markers, in the table within this article.
While quite a few tumor markers are available and have been found to be clinically useful, others are available but not ordered frequently because they have been found to be less sensitive and/or specific. Still others are currently used only in research settings and continue to be evaluated in clinical trials. With ongoing research, and as the field continues to evolve, it is likely that more tumor markers with greater effectiveness will come on the market in the coming years, eventually replacing less useful ones.
While tumor marker tests can provide very useful information, they do have limitations:
- Many tumor markers may also be elevated in persons with conditions or diseases other than cancer.
- Some tumor markers are specific for a particular type of cancer, while others are seen in several different types of cancer.
- Not every person with a particular type of cancer will have an elevated level of the corresponding tumor marker.
- Not every cancer has a tumor marker that has been identified as associated with it.
Consequently, tumor markers alone are not diagnostic for cancer; for some types of cancer, they provide additional information that can be considered in conjunction with a patient’s medical history and physical exam as well as other laboratory and/or imaging tests.
How are tumor markers used?
Tumor markers may be used for a variety of purposes. However, they are not typically used alone. Depending on the type of cancer, they may be used in conjunction with a tissue biopsy or a bone marrow or blood smear examination, for example, and/or with other tumor markers. They are not definitive but provide additional information that can be used to help:
- Screen. Because most tumor markers are not sensitive or specific enough, these tests are not well suited for screening the general population; however, a few may be used to screen people who are at high risk because they have a strong family history or specific risk factors for a particular cancer.
- Help diagnose. In a person who has symptoms, tumor markers may be used to help detect the presence of cancer and help differentiate it from other conditions with similar symptoms.
- Stage. If a person does have cancer, tumor marker elevations can be used to help determine whether the cancer has spread (metastasized) to other tissues and organs and to what extent.
- Determine prognosis. Some tumor markers can be used to help determine how aggressive a cancer is likely to be.
- Guide choice of treatment. A few tumor markers provide information about which treatments might be effective against a person’s cancer. This is a growing area of research. For more information, see the article Genetic Tests for Targeted Cancer Therapy.
- Monitor success of treatment and detect recurrence. 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.) One of the most important uses for tumor markers, along with guiding treatment, 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.)
Examples of tumor markers that are used in each of these ways are provided in the table below.
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Table of Examples of Tumor Markers
Tumor markers often have more than one purpose and may be associated with more than one type of cancer. This table lists examples of tumor markers found on this web site and their different uses. Click on the tumor marker to go to the test article for more details on a particular marker.
|Tumor marker||Associated cancer(s)||Usual sample||Use(s)||Comments|
|AFP (Alpha-feto protein)||Certain liver, ovarian, testicular||Blood||Helps diagnose, monitors treatment and for recurrence||Also elevated during pregnancy and hepatitis|
|ALK gene rearrangements||Non-small cell lung cancer, anaplastic large cell lymphoma||Tissue||Guides treatment||Helps guide targeted therapy|
|B-cell immunoglobulin gene rearrangement||B-cell lymphoma||Bone marrow, tissue, body fluid, blood||Helps diagnose, monitor treatment and for recurrence||Detects characteristic changes in specific genes in B-cells|
|Beta-2 microglobulin||Multiple myeloma, some leukemias, and lymphomas||Blood, urine, CSF||Determines prognosis, monitors treatment & for recurrence||Elevated in other conditions, such as kidney disease|
|BCR-ABL||Chronic myleloid leukemia (CML) and BCR-ABL-positive acute lymphocytic leukemia (ALL)||Blood, bone marrow||Helps diagnose, monitors treatment and for recurrence|
|CA 15-3 (Cancer antigen 15-3 and CA 27.29 are two different tests for same marker||Breast||Blood||Monitors treatment and for recurrence||Also elevated in other cancers (lung, ovarian), benign breast conditions, endometriosis, hepatitis|
|CA 19-9 (Cancer antigen 19-9)||Pancreatic, sometimes bile ducts, gallbladder, stomach, colon||Blood||Monitors treatment and for recurrence||Also elevated in other forms of digestive tract cancer and non-cancer, thyroid disease, pancreatitis, bile duct obstruction, inflammatory bowel disease|
|CA-125 (Cancer antigen 125)||Ovarian||Blood||Helps diagnose, monitors treatment and for recurrence||Also elevated with other cancers (e.g., endometrial, peritoneal, fallopian tube), PID, uterine fibroids, endometriosis, pregnancy)|
|Calcitonin||Medullary thyroid carcinoma (MTC) and C-cell hyperplasia||Blood||Helps diagnose, monitors treatment and for recurrence||Also elevated with other cancers (lung, leukemias) but not used to detect these|
|CEA (Carcino-embryonic antigen)||Colon, pancreatic, lung, breast, ovarian, medullary thyroid, others||Blood||Stages cancer, determines prognosis, monitors treatment and for recurrence||Elevated in conditions such as RA, hepatitis, COPD, colitis, pancreatitis, and in cigarette smokers|
|Chromogranin A (CgA)||Neuroendocrine tumors (carcinoid tumors, neuroblastoma)||Blood||Helps diagnose, monitors treatment and for recurrence||May be most sensitive tumor marker for carcinoid tumors|
|DCP (Des-gamma-carboxy prothrombin)||Hepatocellular carcinoma (HCC)||Blood||Monitors treatment and for recurrence||May be used with imaging study, AFP, AFP-L3%|
|EGFR mutation||Non-small cell lung cancer, sometimes head and neck||Tissue||Determines prognosis, guides treatment||Helps guide targeted therapy|
|Estrogen and Progesterone receptors||Breast||Tissue||Determines prognosis, guides treatment||Increased in hormone-dependent cancer|
|Fibrin/Fibrinogen||Bladder||Urine||Monitors treatment, detects recurrence|
|Gastrin||G-cell hyperplasia, gastrin-producing tumor (gastrinoma)||Blood||Helps diagnose, monitors treatment and for recurrence||Also used to help diagnose Zollinger-Ellison syndrome|
|hCG (Human chorionic gonadotropin, also called Beta-hCG)||Testicular and trophoblastic disease, germ cell tumors, choriocarcinoma||Blood, urine||Helps diagnose, monitors treatment and for recurrence||Elevated in pregnancy|
|HER2||Breast, gastric, esophageal||Tissue||Determines prognosis, guides treatment||Helps guide treatment with drugs that work against HER2 receptors on cancer cells|
|JAK2 mutation||Certain types of leukemia, myeloproliferative neoplasms, especially polycythemia vera||Blood, bone marrow||Helps diagnose||Detects gene mutations associated with conditions listed|
|KRAS mutation||Colon, non-small cell lung cancer||Tissue||Determines prognosis, guides treatment||Helps guide targeted therapy|
|Lactate dehydrogenase (LD, LDH)||Testicular and other germ cell tumors||Blood||Stages cancer, guides treatment, monitors treatment and for recurrence||Elevated in a wide variety of conditions; may be used in other cancers (e.g., lymphoma, melanoma, neuroblastoma)|
|Monoclonal immunoglobulins||Multiple myeloma and Waldenstroms macroglobulinemia||Blood, urine||Helps diagnose, monitors treatment and for recurrence||Usually detected by protein electrophoresis or serum free light chains|
|PSA (Prostate specific antigen)||Prostate||Blood||May be used for screening, helps diagnose, monitors treatment and for recurrence||Also elevated in benign prostatic hyperplasia (BPH), prostatitis; may be used for screening|
|SMRP (Soluble mesothelin-related peptides)||Mesothelioma (rare cancer associated with asbestos exposure)||Blood||Monitors treatment and for recurrence||Often used in conjunction with imaging tests|
|T-cell receptor gene rearrangement||T-cell lymphoma||Bone marrow, tissue, body fluid, blood||Helps diagnose, monitors treatment and for recurrence||Detects characteristic changes (rearrangements) in specific genes in T-cells|
|Thyroglobulin||Thyroid||Blood, tissue||Monitors treatment and for recurrence||Used after thyroid is removed to evaluate treatment|
|Breast cancer gene expression tests (e.g., Oncotype DX® and MammaPrint®)||Breast||Tissue||Monitors treatment and for recurrence; helps guide treatment||Evaluate risk of recurrence; help determine whether some people with breast cancer can avoid chemotherapy|
Sources Used in Current Review
(November 4, 2015) National Cancer Institute. Tumor Markers. Available online at https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet. Accessed January 2019.
(7 November 2018) MedlinePlus. Tumor Marker Tests. Available online at https://medlineplus.gov/lab-tests/tumor-marker-tests/. Accessed January 2019.
(May 2018) Cancer.Net. Tumor Markers Tests. Available online at https://www.cancer.net/navigating-cancer-care/diagnosing-cancer/tests-and-procedures/tumor-marker-tests. Accessed January 2019.
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Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, Sixth Edition. St. Louis, Missouri. Copyright © 2018 by Elsevier. Chapter 31, Tumor Markers.
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