A tumor marker is a substance that is produced by the body in response to cancer, or is produced by the cancer itself. Some of these markers are specific to one cancer, while others are seen in several types of cancer. These markers are generally used to evaluate the patient's response to treatment or to monitor for recurrence (return of the cancer after treatment). There are non-cancerous conditions that can cause markers to be elevated, so these must also be considered when interpreting the test results. Tumor markers can be used in conjunction with other tests (scans, biopsies, etc.) to help diagnose a patient who has symptoms suspicious for cancer. Some markers can help physicians to determine prognosis and treatment.
Ideally, markers could be used as a screening tool for the general public. The goal of a screening test is to diagnose cancer early, when it is the most treatable and before it has had a chance to grow and spread. So far, the only tumor marker to gain wide acceptance as a screening tool is the Prostate Specific Antigen (PSA) for prostate cancer. Other markers are either not specific enough (too many false positives, leading to expensive and unnecessary follow-up testing), or they are not elevated early enough in the life of the cancer, and therefore the cancer cannot be detected any earlier than when symptoms begin to appear. Keep in mind that some substances used as markers are produced naturally in the body, and a "normal" level is not always zero.
Tumor markers are not elevated in all cases of the cancers they are used for, and they are not helpful in all patients. For instance, carcinoembryonic antigen (CEA) is used to detect colon cancer recurrence, yet it is only produced in 70-80% of colon cancer cases. In addition, only 25% of cases that are limited to the colon (early stages) have elevated CEA, so it cannot always detect colon cancer in its early stages, when cure rates are best. The bottom line is, tumor markers can be very helpful in following response to treatment and recurrence, but they cannot replace physical examination, evaluation of symptoms, and radiologic studies (CT scan, MRI, PET, etc.).
The following is a table of the most commonly used tumor markers, the cancers they can be present in, non-cancerous conditions that can elevate them, and the range of normal results. In cases where the half-life is listed, this should be considered when checking levels. For example, the PSA half-life is 2-3 days, so if the level were checked the day after surgical removal of the prostate, it would still be elevated. If the level were checked a week later, the result should be zero, or very close to zero, if no prostate tissue remains.
| Tumor Marker | Cancers Associated With Elevated Results | Non-Cancerous Elevations | "Normal" Results |
| (** indicates the most common association, if one exists) | |||
| Alpha-fetoprotein (AFP) (blood serum marker) | Germ cell cancers of ovaries & testes** (Non-seminomatous, particularly embryonal and yolk sac, testicular cancers) Some primary liver cancers (hepatocellular) | Pregnancy (clears after birth), liver disease (hepatitis, cirrhosis, toxic liver injury), inflammatory bowel disease | Low levels present in both men & non-pregnant women (0-15 IU/ml); generally results >400 are caused by cancer (Half-life 4-6 days) |
| Beta-Human Chorionic Gonadotropin (B-HCG) (blood serum marker) | Germ cell tumors Gestational trophoblastic disease | Pregnancy, marijuana use, hypogonadism (testicular failure), cirrhosis, inflammatory bowel disease, duodenal ulcers | In men: < 2.5 U/ml In non-pregnant women: < 5.0 U/ml |
| Bence-Jones Proteins (urine) or Monoclonal Immunoglobulins (blood) | Multiple Myeloma** Waldenstrom's Macroglobulinemia Chronic Lymphocytic Leukemia | Amyloidosis | Generally, a value of 0.03-0.05 mg/ml is significant for early disease |
| Bladder Tumor Antigen (BTA) (urine marker) | Bladder cancer** Cancer of kidney or ureters | Invasive procedure or infection of bladder or urinary tract | None normally detected |
| CA 15-3 (Carbohydrate antigen 15-3) (blood serum marker) | Breast** (often not elevated in early stages of breast cancer) Lung, ovarian, endometrial, bladder, gastrointestinal | Liver disease (cirrhosis, hepatitis), lupus, sarcoid, tuberculosis, non-cancerous breast lesions | < 31 U/ml (30% of patients have an elevated CA 15-3 for 30-90 days after treatment, so wait 2-3 months after starting new treatment to check) |
| CA 19-9 (Carbohydrate antigen 19-9) (blood serum marker) | Pancreas** and colorectal** Liver, stomach and biliary tree cancers | Pancreatitis, ulcerative colitis, inflammatory bowel disease, inflammation or blockage of the bile duct | < 37 U/ml > 120 U/ml is generally caused by tumor |
| CA 125 (Carbohydrate antigen 125) (blood serum marker) | Ovarian cancer** Breast, colorectal, uterine, cervical, pancreas, liver, lung | Pregnancy, menstruation, endometriosis, ovarian cysts, fibroids, pelvic inflammatory disease, pancreatitis, cirrhosis, peritonitis, pleural effusion, following surgery or paracentesis | 0-35 U/ml |
| CA 27.29 (Carbohydrate antigen 27.29) (blood serum marker) | Breast** (best used to detect recurrence or metastasis) Colon , gastric, liver, lung, pancreatic, ovarian, prostate cancers | Ovarian cysts, liver and kidney disorders, non-cancerous (benign) breast problems | < 40 U/ml Generally, levels > 100 U/ml signify cancer (30% of patients have elevated CA 27.29 for 30-90 days after treatment, so wait 2-3 months after starting new treatment to check) |
| Carcinoembryonic antigen (CEA) (blood serum marker) | Colorectal cancers ** Breast, lung, gastric, pancreatic, bladder, kidney, thyroid, head & neck, cervical, ovarian, liver, lymphoma, melanoma | Cigarette smoking, pancreatitis, hepatitis, inflammatory bowel disease, peptic ulcer disease, hypothyroidism, cirrhosis, COPD, biliary obstruction | <2.5 ng/ml in non-smokers <5 ng/ml in smokers Generally, > 100 signifies metastatic cancer |
| 5-HIAA (5-Hydroxy-Indol Acetic Acid) (24 hour urine collection) | Carcinoid tumors | Celiac & tropical sprue, Whipple's disease, dietary: walnuts, pecans, bananas, avocados, eggplants, pineapples, plums & tomatoes; medications: acetaminophen, aspirin and guaifenesin | Normal 6-10 mg over 24 hours |
| Lactic dehydrogenase (LDH) (blood serum marker) | Lymphoma, melanoma, acute leukemia, seminoma (germ cell tumors) | Hepatitis, MI (heart attack), stroke, anemia (pernicious & thalassemia), muscular dystrophy, certain medications (narcotics, aspirin, anesthetics, alcohol), muscle injury | Normal values are 100-333 u/l |
| NMP 22 (urinary marker) | Bladder cancer** | BPH (benign prostatic hypertrophy), prostatitis | Normal < 10 U/ml |
| PAP (Prostatic acid phosphatase) (blood serum marker) | Metastatic prostate cancer** Myeloma, lung cancer, osteogenic sarcoma | Prostatitis, Gaucher's disease, osteoporosis, cirrhosis, hyperparathyroidism, prostatic hypertrophy | Normal : 0.5 to 1.9 u/l |
| PSA (Prostate specific antigen) | Prostate | BPH (benign prostatic hypertrophy), nodular prostatic hyperplasia, prostatitis, prostate trauma or inflammation | Normal < 4 ng/ml (half life 2-3 days) |
| Urine Catecholamines: VMA (Vanillylmandelic Acid) (24 hour collection of urine; it is a catecholamine metabolite) | Neuroblastoma** Pheochromocytoma, ganglioneuroma, rhabdomyosarcoma, PNET | Dietary intake (bananas, vanilla, tea, coffee, ice cream, chocolate), medications (tetracyclines, methyldopa, MAOIs) | 8 – 35 mmols over 24 hours |
| HVA (homovanillic acid) (24 hour collection of urine; it is a catecholamine metabolite) | Neuroblastoma** | Same as VMA, in addition: psychosis, major depression, dopamine (a medication) | Up to 40 mmols over 24 hours |
References
Abeloff, M., Armitage, J., Niederhuber, J., Kastan, M. & McKenna, G. (Eds.): Clinical Oncology (2004). Elsevier, Philadelphia , PA.
Perkins GL, Slater ED, Sanders GK, Prichard JG. Serum tumor markers. Am Fam Physician 2003;68:1075-82.
Sanchez Yamamoto D, Hallquist Viale P, Roesser K, Lin A. The clinical use of tumor makers in select cancers: are you confident enough to discuss them with your patients? Oncol Nurs Forum 2005;32:1013-22; quiz 1023-4.
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