1. What are tumor markers?

   Tumor markers are substances produced by tumor cells or by other cells of the body in response to cancer or certain benign (noncancerous) conditions. These substances can be found in the blood, in the urine, in the tumor tissue, or in other tissues. Different tumor markers are found in different types of cancer, and levels of the same tumor marker can be altered in more than one type of cancer. In addition, tumor marker levels are not altered in all people with cancer, especially if the cancer is early stage. Some tumor marker levels can also be altered in patients with noncancerous conditions.

   To date, researchers have identified more than a dozen substances that seem to be expressed abnormally when some types of cancer are present. Some of these substances are also found in other conditions and diseases. Scientists have not found markers for every type of cancer.

2. What are risk markers?

   Some people have a greater chance of developing certain types of cancer because of a change, known as a mutation or alteration, in specific genes. The presence of such a change is sometimes called a risk marker. Tests for risk markers can help the doctor to estimate a person’s chance of developing a certain cancer. Risk markers can indicate that cancer is more likely to occur, whereas tumor markers can indicate the presence of cancer (1).

3. How are tumor markers used in cancer care?

   Tumor markers are used in the detection, diagnosis, and management of some types of cancer. Although an abnormal tumor marker level may suggest cancer, this alone is usually not enough to diagnose cancer. Therefore, measurements of tumor markers are usually combined with other tests, such as a biopsy, to diagnose cancer.

   Tumor marker levels may be measured before treatment to help doctors plan appropriate therapy. In some types of cancer, tumor marker levels reflect the stage (extent) of the disease. (More information about staging is available in the National Cancer Institute (NCI) fact sheet Staging: Questions and Answers, which can be found at http://www.cancer.gov/cancertopics/factsheet/Detection/staging on the Internet.)

   Tumor marker levels also may be used to check how a patient is responding to treatment. A decrease or return to a normal level may indicate that the cancer is responding to therapy, whereas an increase may indicate that the cancer is not responding. After treatment has ended, tumor marker levels may be used to check for recurrence (cancer that has returned).

4. How and when are tumor markers measured?

   The doctor takes a blood, urine, or tissue sample and sends it to the laboratory, where various methods are used to measure the level of the tumor marker.

   If the tumor marker is being used to determine whether a treatment is working or if there is recurrence, the tumor marker levels are often measured over a period of time to see if the levels are increasing or decreasing. Usually these “serial measurements” are more meaningful than a single measurement. Tumor marker levels may be checked at the time of diagnosis; before, during, and after therapy; and then periodically to monitor for recurrence.

5. Does the NCI have guidelines for the use of tumor markers?

   No, the NCI does not have such guidelines. However, some organizations do have these guidelines for some types of cancer.

   The American Society of Clinical Oncology (ASCO), a nonprofit organization that represents more than 25,000 cancer professionals worldwide, has published clinical practice guidelines on a variety of topics, including tumor markers for breast and colorectal cancer. These guidelines, called Patient Guides, are available on the ASCO Web site at http://www.cancer.net/patient/ASCO+Resources/Patient+Guides on the Internet.

   The National Comprehensive Cancer Network® (NCCN), which is also a nonprofit organization, is an alliance of cancer centers. The NCCN provides Patient Guidelines, which include tumor marker information for several types of cancer. Most of the guidelines are available in English and Spanish versions. The Patient Guidelines are on the NCCN’s Web site at http://www.nccn.org/patients/patient_gls.asp on the Internet.

   The National Academy of Clinical Biochemistry (NACB) is a professional organization dedicated to advancing the science and practice of clinical laboratory medicine through research, education, and professional development. The Academy publishes Practice Guidelines and Recommendations for Use of Tumor Markers in the Clinic, which focuses on the appropriate use of tumor markers for specific cancers. More information can be found at http://direct.aacc.org/ProductCatalog/Product.aspx?ID=2131 on the Internet.

6. Can tumor markers be used as a screening test for cancer?

   Screening tests are a way of detecting cancer early, before there are any symptoms. For a screening test to be helpful, it should have high sensitivity and specificity. Sensitivity refers to the test’s ability to identify people who have the disease. Specificity refers to the test’s ability to identify people who do not have the disease. Most tumor markers are not sensitive or specific enough to be used for cancer screening.

   Even commonly used tests may not be completely sensitive or specific. For example, prostate-specific antigen (PSA) levels are often used to screen men for prostate cancer, but this is controversial. It is not yet known if early detection using PSA screening actually saves lives. Elevated PSA levels can be caused by prostate cancer or benign conditions, and most men with elevated PSA levels turn out not to have prostate cancer. Moreover, it is not clear if the benefits of PSA screening outweigh the risks of follow-up diagnostic tests and cancer treatments. (More information about PSA screening is available in the NCI fact sheet The Prostate-Specific Antigen (PSA) Test: Questions and Answers, which can be found at http://www.cancer.gov/cancertopics/factsheet/Detection/PSA on the Internet.)

   Another tumor marker, CA 125, is sometimes used to screen women who have an increased risk for ovarian cancer. Scientists are studying whether measurement of CA 125, along with other tests and exams, is useful to find ovarian cancer before symptoms develop. So far, CA 125 measurement is not sensitive or specific enough to be used to screen all women for ovarian cancer. Mostly, CA 125 is used to monitor response to treatment and check for recurrence in women with ovarian cancer.

7. What research is being done in this field?

   Scientists continue to study tumor markers and their possible role in the early detection and diagnosis of cancer. The NCI is currently conducting the Prostate, Lung, Colorectal, and Ovarian Cancer screening trial, or PLCO trial, to determine if certain screening tests reduce the number of deaths from these cancers. Along with other screening tools, PLCO researchers are studying the use of PSA to screen for prostate cancer and CA 125 to screen for ovarian cancer. Final results from this study are expected in several years.

   Cancer researchers are turning to proteomics (the study of protein shape, function, and patterns of expression) in hopes of developing better cancer screening and treatment options. Proteomics technology is being used to search for proteins that may serve as markers of disease in its early stages or to predict the effectiveness of treatment or the chance of the disease returning after treatment has ended. More information about proteomics can be found in Proteomics and Cancer: Fact Sheet, which is available at http://www.cancer.gov/cancertopics/factsheet/proteomicsqa on the Internet.

   Scientists are also evaluating patterns of gene expression (the step required to translate what is in the genes to proteins) for their ability to predict a patient’s prognosis (likely outcome or course of disease) or response to therapy. NCI’s Early Detection Research Network is developing a number of genomic- and proteomic-based biomarkers, some of which are being validated. More information about this program can be found at http://edrn.nci.nih.gov/ on the Internet.

   Information about clinical trials is available from the NCI’s Cancer Information Service (see below) or on the clinical trials page of the NCI’s Web site at http://www.cancer.gov/clinicaltrials on the Internet. In addition, PDQ®, the NCI’s comprehensive cancer information database, contains cancer information summaries that can be found at http://www.cancer.gov/cancerinfo/pdq/ on the Internet.

Selected Reference

1. Bigbee W, Herberman RB. Tumor markers and immunodiagnosis. In: Bast RC Jr., Kufe DW, Pollock RE, et al., editors. Cancer Medicine. 6^th ed. Hamilton, Ontario, Canada: BC Decker Inc., 2003.

Related NCI materials and Web pages:

• National Cancer Institute Fact Sheet 3.62, Genetic Testing for BRCA1 and BRCA2: It’s Your Choice ¹
  (http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA)
• National Cancer Institute Fact Sheet 5.27, Interpreting Laboratory Test Results ²
  (http://www.cancer.gov/cancertopics/factsheet/Detection/laboratory-tests)
• National Cancer Institute Fact Sheet 5.29, The Prostate-Specific Antigen (PSA) Test: Questions and Answers ³
  (http://www.cancer.gov/cancertopics/factsheet/Detection/PSA)
• National Cancer Institute Fact Sheet 5.32, Staging: Questions and Answers ⁴
  (http://www.cancer.gov/cancertopics/factsheet/Detection/staging)
• National Cancer Institute Fact Sheet 8.2, Understanding Prognosis and Cancer Statistics: Questions and Answers ⁵
  (http://www.cancer.gov/cancertopics/factsheet/support/prognosis-stats)
• What You Need To Know About™ Cancer—An Overview ⁶
  (http://www.cancer.gov/cancertopics/wyntk/overview)

For more help, contact:

NCI's Cancer Information Service
Telephone (toll-free): 1–800–4–CANCER (1–800–422–6237)
TTY (toll-free): 1–800–332–8615
LiveHelp^® online chat: https://cissecure.nci.nih.gov/livehelp/welcome.asp

Glossary Terms

A change resulting in something that is different from the original.

Not cancerous. Benign tumors may grow larger but do not spread to other parts of the body.

A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule.

The removal of cells or tissues for examination by a pathologist. The pathologist may study the tissue under a microscope or perform other tests on the cells or tissue. There are many different types of biopsy procedures. The most common types include: (1) incisional biopsy, in which only a sample of tissue is removed; (2) excisional biopsy, in which an entire lump or suspicious area is removed; and (3) needle biopsy, in which a sample of tissue or fluid is removed with a needle. When a wide needle is used, the procedure is called a core biopsy. When a thin needle is used, the procedure is called a fine-needle aspiration biopsy.

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

A substance that may be found in high amounts in the blood of patients with certain types of cancer, including ovarian cancer. CA-125 levels may also help monitor how well cancer treatments are working or if cancer has come back. Also called cancer antigen 125.

A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord.

CIS. The Cancer Information Service is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER (1-800-422-6237), or by using the LiveHelp instant-messaging service at https://cissecure.nci.nih.gov/livehelp/welcome.asp. Also called CIS.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Guidelines developed to help health care professionals and patients make decisions about screening, prevention, or treatment of a specific health condition.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called a clinical study.

Having to do with the colon or the rectum.

Cancer that develops in the colon (the longest part of the large intestine) and/or the rectum (the last several inches of the large intestine before the anus).

The process of identifying a disease, such as cancer, from its signs and symptoms.

A method used to identify a disease.

The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

A diagnostic indication that disease may develop.

Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

Cancer that forms in tissues of the ovary (one of a pair of female reproductive glands in which the ova, or eggs, are formed). Most ovarian cancers are either ovarian epithelial carcinomas (cancer that begins in the cells on the surface of the ovary) or malignant germ cell tumors (cancer that begins in egg cells).

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

The likely outcome or course of a disease; the chance of recovery or recurrence.

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

Cancer that forms in tissues of the prostate (a gland in the male reproductive system found below the bladder and in front of the rectum). Prostate cancer usually occurs in older men.

PSA. A substance produced by the prostate that may be found in an increased amount in the blood of men who have prostate cancer, benign prostatic hyperplasia, or infection or inflammation of the prostate. Also called PSA.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The study of the structure and function of proteins, including the way they work and interact with each other inside cells.

Cancer that has recurred (come back), usually after a period of time during which the cancer could not be detected. The cancer may come back to the same place as the original (primary) tumor or to another place in the body. Also called recurrent cancer.

In medicine, an improvement related to treatment.

Checking for disease when there are no symptoms. Since screening may find diseases at an early stage, there may be a better chance of curing the disease. Examples of cancer screening tests are the mammogram (breast), colonoscopy (colon), Pap smear (cervix), and PSA blood level and digital rectal exam (prostate). Screening can also include checking for a person’s risk of developing an inherited disease by doing a genetic test.

When referring to a medical test, sensitivity refers to the percentage of people who test positive for a specific disease among a group of people who have the disease. No test has 100% sensitivity because some people who have the disease will test negative for it (false negatives).

When referring to a medical test, specificity refers to the percentage of people who test negative for a specific disease among a group of people who do not have the disease. No test is 100% specific because some people who do not have the disease will test positive for it (false positive).

The extent of a cancer in the body. Staging is usually based on the size of the tumor, whether lymph nodes contain cancer, and whether the cancer has spread from the original site to other parts of the body.

Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. It is important to know the stage of the disease in order to plan the best treatment.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Treatment.

A group or layer of cells that work together to perform a specific function.

A substance that may be found in tumor tissue or released from a tumor into the blood or other body fluids. A high level of a tumor marker may mean that a certain type of cancer is in the body. Examples of tumor markers include CA 125 (in ovarian cancer), CA 15-3 (in breast cancer), CEA (in ovarian, lung, breast, pancreas, and gastrointestinal tract cancers), and PSA (in prostate cancer).

Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra.