In the Spotlight May 03, 2000 Tumor Markers By Lee Phillips, MD Personal MD.com Contributing Editor

Tumor markers are substances that can be detected in the blood, urine, or body tissues of people with certain types of cancer. They are produced either by the tumor itself or by the body in response to the presence of cancer.

Some tumor marker levels are measured before treatment to help doctors plan the best therapy. In some types of cancer, tumor marker levels reflect the extent (stage) of the cancer and can be useful in predicting how well the disease will respond to treatment.

Tumor marker levels may also be measured during treatment to monitor a patient's response to treatment. A decrease or return to normal in the level of a tumor marker may indicate that the cancer has responded favorably to therapy. If the tumor marker level rises, it may indicate that the cancer is growing. Measurements of tumor marker levels may also be used after treatment has ended as a way to check for recurrence.

The ideal tumor marker for cancer would be very "specific", meaning it would occur only in patients with a particular cancer. It would also be "sensitive" reflecting the extent (stage) of the cancer. At this point in time, tumor marker levels alone are not yet sophisticated enough to be used as a screening test for healthy people at low-risk for cancer for the following reasons:

• Tumor marker levels can be elevated in people without cancer.
• Tumor marker levels are not elevated in every person with cancer--especially in the early stages of the disease.
• Many tumor markers are not specific to a particular type of cancer; the level of a tumor marker can be raised by more than one type of cancer.
  

However, tumor marker levels can be useful--when used along with x-rays or other tests--in the detection and diagnosis of some types of cancer in the people known to have a higher risk for cancer.

Here are some examples of markers and how they are being used today.

Prostate-Specific Antigen

Prostate-specific antigen (PSA) is made by normal and abnormal prostates of all adult males. By the age of 50 most men will have an enlarged prostate and will make more PSA than a younger man. Elevated PSA levels may also be found in the blood of men with prostatitis (inflammation of the prostate), benign prostatic hyperplasia (BPH), or prostate cancer, While PSA does not allow doctors to distinguish between BPH, prostatitis, and cancer, an elevated PSA level may indicate that other tests are necessary to determine whether cancer is present. Doctors generally look for the rate of change of PSA over time, rather than focusing on a single elevated result.

CA 125

Ovarian cancer cells can produce CA 125. Not all women with elevated CA 125 levels have ovarian cancer. Other cancers and non-cancerous conditions, such as menstruation and pregnancy may also elevate CA 125 levels.

Carcinoembryonic Antigen

Carcinoembryonic antigen (CEA) is normally found in small amounts in the blood of most healthy people. Elevated CEA levels can also occur in patients with non-cancerous conditions, including inflammatory bowel disease, pancreatitis, and liver disease. Tobacco use can also contribute to higher-than-normal levels of CEA. For these reasons CEA is not used to diagnose cancer. The primary use of CEA is in monitoring colorectal and other cancers, especially when the disease has spread.

Alpha-Fetoprotein

Alpha-fetoprotein (AFP) is normally produced by a developing fetus. AFP levels begin to decrease soon after birth and are usually undetectable in the blood of healthy adults (except during pregnancy). An elevated level of AFP strongly suggests either liver cancer or germ cell cancer (cancer that begins in the cells that give rise to eggs or sperm) of the ovary or testicle.

Human Chorionic Gonadotropin

Human chorionic gonadotropin (HCG) is normally produced by the placenta during pregnancy. In fact, HCG is sometimes used as a pregnancy test because it increases early in the first trimester. Elevated HCG levels may also indicate the presence of cancers of the testis, ovary, liver, stomach, pancreas, and lung. Pregnancy and marijuana use can also cause elevated HCG levels.

CA 19-9

CA 19-9 is used to follow and look for signs of recurrence of colon and rectal cancers. It may also be used to follow pancreatic, stomach, and bile duct cancer. Researchers have discovered that, in those who have pancreatic cancer, higher levels of CA 19-9 tend to be associated with more advanced disease. Non-cancerous conditions that may elevate CA 19-9 levels include gallstones, pancreatitis, cirrhosis of the liver, and cholecystitis.

CA 15-3

CA 15-3 is a commonly used marker to follow the course of treatment in women diagnosed with advanced breast cancer and metastasis to the bone. CA 15-3 levels are rarely elevated in women with early stage breast cancer.

CA 27-29

Similar to the CA 15-3 antigen, CA 27-29 is found in the blood of most breast cancer patients. CA 27-29 levels may be used in conjunction with other tests to check for recurrence in women previously treated for stage II and stage III breast cancer.

Neuron-Specific Enolase

Neuron-specific enolase (NSE) has been detected in patients with neuroblastoma; small cell lung cancer; Wilms' tumor; melanoma; and cancers of the thyroid, kidney, testicle, and pancreas. However, studies of NSE as a tumor marker have concentrated primarily on patients with neuroblastoma and small cell lung cancer. Measurement of NSE level in patients with these two diseases can provide information about the extent of the disease and the patient's prognosis, as well as about the patient's response to treatment.