Tumor Markers

About Tumor Markers

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.

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).

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 RequirementsExit Disclaimer, which focuses on the appropriate use of tumor markers for specific cancers.

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.

Common Tumor Markers

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

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