Tumor markers are substances, such as proteins, biochemicals, or enzymes, produced by tumor cells or by the body in response to tumor cells. As tumor cells multiply, cancer spreads, and tissue is damaged, these substances increase and leak into the bloodstream. Tumor marker levels in blood help evaluate people for certain types of cancer.
Tumor marker levels provide evidence about the likelihood of undiagnosed cancer or the status of treated cancer without the expense and discomfort of ultrasound, x-ray, or biopsy procedures. Tumor marker levels are used to screen for and diagnose cancer, predict a person's prognosis, monitor treatment, and watch for cancer recurrence.
Tumor markers associated with common cancers include: AFP, Beta-HCG, CA 15-3, CA 19-9, CA 27.29, CA 125, CEA, and PSA. Some tumor markers are associated with many types of cancer; others, with as few as one. Some tumor markers are always elevated in specific cancers; others are less predictable.
A tumor marker test's ability to screen for and diagnose a specific type of cancer depends on its sensitivity and specificity. A test that is 100% sensitive has no false negatives. It is positive or increased in every person who has that type of cancer. A test that is 100% specific has no false positives. It is negative or decreased in every person who does not have that type of cancer.
Most tumor markers are neither sensitive nor specific enough to screen for or diagnose cancer without the support of other clinical findings. Increased levels are not found in all people with a specific type of cancer, yet may be found in some people without that type of cancer. In addition, tumor marker levels often do not increase until the person experiences symptoms.
Once cancer is diagnosed, tumor marker levels help determine the amount of cancer present. Higher levels usually indicate more advanced cancer and a worse prognosis. The person and his or her physician use this information to choose between more or less aggressive treatments.
Monitoring cancer treatment is the most common use of tumor markers. As cancer is reduced, levels decrease. Stable or increasing levels indicate the cancer is not responding to treatment.
The choice of tumor marker to use for monitoring is important. Only a marker elevated before treatment can be used to monitor a person during or after treatment. Timing of the tests is also important. Each tumor marker has a unique lifespan in the blood. To monitor a treatment's success, enough time must have passed for the initial marker to be cleared from the blood. Tests done too soon may be falsely elevated because the marker produced by the untreated cancer is still present.
Watching for cancer recurrence is another common reason for tumor marker testing. Periodic testing can detect a recurrence often months earlier than could an ultrasound, x-ray, or physical examination.
Tumor marker tests usually are done by combining a sample of blood with a substance containing antibodies to the tumor markers. These antibodies bind to the markers. Another substance is added, often a radioactive substance, to measure the amount of bound marker and antibodies. From this measurement, the amount of tumor marker is calculated.
Conclusions based on tumor marker tests are seldom based on one test result but on a series of test results, called serial measurements. A series of increasing or decreasing values is more significant than a single value.
Tumor marker testing is currently the object of much research. Their use is directed by approval from the Food and Drug Administration (FDA) and guidelines established by organizations such as the American Society of Clinical Oncology and the American Cancer Society.
Tumor marker test results are available within several days. Insurance coverage for markers still in the research stage for particular uses may vary with the company and individual policy.
AFP is a protein normally made by only fetal tissue. When certain types of cells become cancerous, they revert to a fetal form and begin making AFP. Increased levels are associated most strongly with liver, testicular, and ovarian cancer. Seventy-percent of people with liver cancer have increased AFP levels. Levels indicate the extent of cancer. Serial measurements monitor treatment response.
Pregnant women and people with noncancerous liver conditions such as cirrhosis and hepatitis have moderately increased levels.
Beta-subunit human chorionic gonadotropin (Beta-HCG)
The beta-subunit of the hormone HCG is a marker for testicular cancer and cancers that begin in placental cells called trophoblasts. Women with choriocarcinoma (a cancer originating in the placenta following pregnancy) or molar pregnancy (a tumor inside the uterus) have increased levels of Beta-HCG, as do 70% of men with testicular cancer. Serial measurements monitor the progress and treatment of these cancers.
Cancer antigen 15-3 (CA 15-3)
CA 15-3 is produced by cells in the breast. Increased levels are associated with breast cancer. Rarely increased in women with early breast cancer, it is used to detect recurrence of cancer in women following treatment or mastectomy.
Cancer antigen 19-9 (CA 19-9)
CA 19-9 helps diagnose pancreatic cancer when combined with other test results and clinical findings. After diagnosis, levels help predict the success of surgery and to monitor the course of the cancer.
Not all people with pancreatic cancer have increased CA 19-9 levels. This marker is associated with a specific blood type. People with pancreatic cancer who are negative for this blood type will not have CA 19-9 in their blood. It is also increased in liver and gastrointestinal cancer and in noncancerous diseases, such as pancreatitis and jaundice.
Breast carcinoma-associated antigen (CA 27.29)
CA 27.29 is a marker for breast cancer. Eighty-percent of women with breast cancer have an increased CA 27.29. Serial measurements monitor treatment response and identify recurrence.
Levels may also be increased in noncancerous breast disease and cancers of other tissues. It is not used to screen for breast cancer because women with small or localized breast tumors often have normal CA 27.29 levels.
Cancer antigen 125 (CA 125)
CA 125 is a protein made by ovarian cells and is a marker for ovarian cancer. Eighty percent of women with ovarian cancer have increased CA 125 levels. Although the test is not sensitive and specific enough to be used for screening, it contributes to a diagnosis when combined with an ultrasound and pelvic examination. After diagnosis and treatment, serial measurements help detect remaining or recurrent cancer. A negative or normal result, however, does not guarantee the absence of cancer.
Women may have increased CA 125 levels during menstruation and pregnancy. Increased levels are also found in pelvic inflammatory disease, endometriosis, pancreatitis, liver disease, and non-ovarian cancers.
Carcinoembryonic antigen (CEA)
CEA is a protein made by fetal tissues, especially liver, intestinal, and pancreatic tissue. It disappears by birth but often reappears when cells from these tissues become cancerous.
CEA is most often associated with colorectal cancer, although it is not present in all people with this cancer. Pre-surgery CEA levels help stage the cancer and plan the surgery. After surgery, serial measurements indicate the surgery's success and watch for early signs of recurrence. When CEA is found in other body fluids, such as spinal fluid, it indicates cancer has spread.
CEA levels may be increased in many types of cancer: gastrointestinal, colorectal, liver, lung, pancreatic, liver, prostate, thyroid, and breast. People with noncancerous conditions, such as cirrhosis or peptic ulcer, and inflammatory intestinal conditions, such as colitis or diverticulitis, also may have increased levels.
Prostate specific antigen (PSA)
PSA is used to screen for prostate cancer. A protein produced by the prostate gland, increased PSA levels are associated with prostate cancer. Men over the age of 50 years are advised to be screened annually for prostate cancer with a digital rectal exam and a PSA test. Men at high risk for prostate cancer, such as African-Americans or those with a family history, should begin screening at age 40. Once a diagnosis of prostate cancer is made, PSA levels help determine the stage of the cancer, monitor the response to treatment, and watch for recurrence.
PSA is also increased in benign prostatic hyperplasia (BPH), an enlarged prostate condition common in older men. Several calculations of the PSA have been developed to help tell the difference between BPH and prostate cancer: PSA density, PSA velocity, and ratio of free to total.
The PSA density calculates the concentration of PSA in the prostate gland. The volume of prostate gland is determined by a procedure called transrectal ultrasound (TRUS). A person with an enlarged prostate, as seen in BPH, has a lower PSA density than a person with prostate cancer. PSA velocity or rate calculates the change in PSA levels over time. A rapid increase in PSA is more likely due to cancer than BPH. The ratio of free PSA to total PSA also helps distinguish BPH from cancer. PSA exists either in a free state or bound to another substance. The percentage of free PSA is greater in BPH than cancer.
PSA levels may increase after ejaculation. Men are recommended to abstain from sexual intercourse or masturbation for 48 hours before the test. PSA levels may also increase after prostate manipulation following the digital rectal exam.
Tumor marker tests require 5-10 mL of blood. A healthcare worker ties a tourniquet on the person's upper arm, locates a vein in the inner elbow region, and inserts a needle into that vein. Vacuum action draws the blood through the needle into an attached tube. Collection of the sample takes only a few minutes.
Discomfort or bruising may occur at the puncture site or the person may feel dizzy or faint. Pressure to the puncture site until the bleeding stops reduces bruising. Warm packs to the puncture site relieve discomfort.
AFP 99% of nonpregnant people have less than 15 ng/mL; 95% have less than 6 ng/mL Beta-HCG Males less than 2.5 IU/L Female less than 5.0 IU/L Postmenopausal female less than 9.0 IU/L CA 15-3 less than 40 U/mL CA 19-9 less than 40 U/mL CA 27.29 less than or equal to 38 U/mL CA 125 less than 35 U/L CEA less than or equal to 5 ng/mL PSA less than 4 ng/mL; PSA levels increase with age. Age-specific values are available.
The meaning of an increased tumor marker level depends on the specific marker, the person's medical history, and why the test was done. Knowledge of the person's history, and additional tests and physical examinations are needed to correctly interpret tumor marker test results.
- AFP (Alpha-fetoprotein)
- A tumor marker associated with liver, testicular, and ovarian cancer.
- Beta-HCG (Beta-human chorionic gonadotropin)
- A tumor marker associated with testicular cancer and tumors, such as choriocarcinoma and molar pregnancies, that begin in placental cells called trophoblasts.
- CA 15-3 (Cancer antigen 15-3)
- A tumor marker associated with breast cancer.
- CA 19-9 (Cancer antigen 19-9)
- A tumor marker associated with pancreatic cancer.
- CA 27.29 (Breast carcinoma-associated antigen)
- A tumor marker associated with breast cancer.
- CA 125 (Cancer antigen 125)
- A tumor marker associated with ovarian cancer.
- CEA (Carcinoembryonic antigen)
- A tumor marker associated with many cancers, especially liver, intestinal, and pancreatic.
- PSA (Prostate specific antigen)
- A tumor marker associated with prostate cancer.
- A test's ability to detect all cases of a disease.
- Serial measurements
- A series of measurements looking for an increase or decrease over time.
- A test's ability to detect only the disease in question.
- Tumor markers
- Substances, such as proteins, biochemicals, or enzymes, produced by tumor cells or by the body in response to tumor cells. Their levels in the blood help evaluate people for certain kinds of cancer.
For Your Information
- American Association of Clinical Chemistry. Tumor Markers: Reclassification, Reimbursement & Recent Advances. Washington DC: American Association of Clinical Chemistry (AACC) Press, 1997.
- Wu, James T. "Diagnosis and Management of Cancer Using Serologic Tumor Markers." In Clinical Diagnosis and Management by Laboratory Methods 19th ed., edited by John B. Henry. Philadelphia: W. B. Saunders Company, 1996, pp. 1064-1080.
- Wu, James T. and Robert M. Makamura. Human Circulating Tumor Markers: Current Concepts and Clinical Applications. Chicago: American Society of Clinical Pathologists Press (ASCP) Press, 1997.
- Aziz, Douglas C. "Clinical Use of Tumor Markers Based on Outcome Analysis. CE-Update--Tumor Markers I." Laboratory Medicine (November, 1996): 760-764.
- Aziz, Douglas C. "Clinical Use of Tumor Markers Based on Outcome Analysis. CE-Update--Tumor Markers II." Laboratory Medicine. (December, 1996): 817-821.
- Coley, Christopher M., et al. "Early Detection of Prostate Cancer. Part I: Prior Probability and Effectiveness of Tests." Annals of Internal Medicine. (March, 1997): 394-406.
- Pamies, Rubens J., and Deborah R. Crawford. "Tumor Markers. An Update." Medical Clinics of North America (January, 1996): 185-199.
- Vashi, Apoorva R. and Joseph E. Oesterling. "Percent Free Prostate-Specific Antigen: Entering a New Era in the Detection of Prostate Cancer." Mayo Clinic Proceedings (April, 1997): 337-344.
- American Cancer Society. 1599 Clifton Road NE, Atlanta , GA, 30329. (800) 227-2345. http://www.cancer.org.
- American Society of Clinical Oncology. 225 Reinekers Lane, Suite 650, Alexandria, VA 22314. (703) 299-0150. http://www.asco.org.
- National Cancer Institute. 9000 Rockville Pike, Building 31, Bethesda, MD 20892. (800) 4-CANCER. http://www.nci.nih.gov.
- National Cancer Institute. "Screening for Ovarian Cancer." May, 1998. http://cancernet.nci.nih.gov/clinpdq/screening/Screening_for_ovarian_cancer_Physician.html. (11 June, 1998).
- National Cancer Institute. "Screening for Prostate Cancer." May, 1998. http://cancernet.nci.nih.gov/clinpdq/screening/Screening_for_prostate_cancer_Physician.html. (11 June, 1998).
Gale Encyclopedia of Medicine. Gale Research, 1999.