CancerPoints

False Positives and False Negatives
in Tumor Marker Blood Tests

 

There are a variety of factors that can affect the accuracy of lab tests. Certain medications can affect the accuracy of some lab tests. For example, taking Tylenol or Naproxen Sodium or 500 mg or more of Vitamin C before a cholesterol test can affect the accuracy of the results. Generally speaking, one should not take any OTC pain medications, smoke tobacco or marijuana, or exercise vigorously before lab tests. Some antibiotics can also interfere with some tests. The following factors are known to lead to false positive or false negative results in tumor marker blood tests.

The other major source of inaccuracies is mishandling of the blood sample by the laboratory, such as failing to refrigerate the blood sample if the test is not done immediately or repeated freezing and thawing of the sample or otherwise disturbing the sample.

Due to the way in which the assays for tumor markers are manufactured, interference from certain rare antibodies, such as human anti-mouse antibody (HAMA) and heterophilic antibody, can yield false positive results in some tests.

The false positive rates for many tumor marker tests are usually around 5%. Also, there have been cases reported in the literature where necrotic tumor is believed to have degraded, releasing entrapped tumor markers, yielding a false positive result. As a result, oncologists typically will not rely on a single test, but instead will want to see persistent high elevation or progression in a series of tests over weeks or months. If your AFP levels were elevated from taking a particular drug daily, one would generally not see progression in serial tests.

If you are concerned about a drug potentially affecting a test, search the web for information about its terminal elimination phase half life. This is an indication of how long it takes for the drug to leave your system. For example, the terminal elimination phase half life for Claritin is 46 hours, so you would need to stop taking it two days before the test. If you have impaired liver or kidney function, however, it can take longer to eliminate the drug from your system. It is best to also check the data sheets for the drug. If you check the data sheets for loratadine, the active ingredient in Claritin, you'll see that they only give warnings about taking it before skin tests for allergies. So you probably don't have to worry about taking it before a tumor marker test. If in doubt, ask the radiologist when you schedule your appointment. Your oncologist can also tell you what you can and can't take before the blood tests.

AntiDiuretic Hormone (ADH)

  • Pneumonia.

Alpha-Fetoprotein (AFP)

  • Smoking tobacco can increase serum AFP levels. Typically AFP increases by about 10% as the result of smoking tobacco. (See Bartels 1993, Bernstein 1989, Cuckle 1990, Thomsen 1983, Spencer 1993.)
  • Binge-drinking of alcohol or long-term alcoholism.
  • Cirrhosis of the liver.
  • Hepatitis and other forms of liver disease.
  • Pregnancy can increase AFP levels.
  • Inflammatory bowel disease.
  • Ataxia Telangiectasia.
  • Wiscott-Aldrich syndrome.
  • Wilson's Disease
  • Hereditary tyrosinosis.
  • VAB-6 chemotherapy. (Disambiguate by looking for elevated markers of liver damage, such as GOT, GPT, and LDH.)

Liver damage can lead to an increase in AFP levels. Consumption of the following, especially at high doses, can lead to liver toxicity:

  • Some dietary supplements, herbal remedies and vitamins can cause liver toxicity, leading to a rise in AFP levels. These include high doses of Vitamin A, Vitamin D, Iron, Amanita species, Asafetida, "Bush" herbal teas, Chaparral, Comfrey, Echinacea, Gentian, Germander, Jin bu huan, Kalms tablets, Mistletoe, Pennyroyal oil, Senna fruit extracts and Valerian.
  • Certain species of mushrooms.
  • Recreational drugs.
  • Acetaminophen (tylenol) consumption.
  • All nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs in particular are potentially problematic.
  • Lipid-lowering agents such as statins and nicotinic acid (niacin, Nicolar).
  • Antidiabetic agents: acarbose (Precose), pioglitazone (Actos), sulfonylureas.
  • Antibiotics: amoxicillin­clavulanate potassium (Augmentin), erythromycin, isoniazid (INH), nitrofurantoin (Furadantin), tetracycline.
  • Antifungal agents: fluconazole (Diflucan), itraconazole (Sporanox), ketoconazole (Nizoral).
  • Retinoids: etretinate (Tegison).
  • Anticonvulsant agents: phenytoin (Dilantin), valproic acid (Depakene).
  • Psychotropic agents: bupropion (Wellbutrin), chlorpromazine (Thorazine), tricyclic antidepressants.
  • Hormones and anabolic steroids: tamoxifen (Nolvadex), testosterone.
  • Others: halothane (Fluothane), methotrexate (Rheumatrex).
  • Exposure to pesticides, solvents and paint thinners.

Pursuing a low-fat diet and exercise can help reduce AFP levels, as can drinking plenty of water. Weight gain can cause AFP levels to rise.

Beta HCG

  • Marijuana use can increase beta HCG levels.
  • Smoking tobacco can decrease beta HCG levels. Typically beta HCG decreases by about 20% as the result of smoking tobacco. (See Bartels 1993, Bernstein 1989, Cuckle 1990, Thomsen 1983, Spencer 1993.)
  • Human anti-mouse antibody (HAMA) or heterophilic antibody.
  • Elevated LH levels due to low testosterone can lead to false positives.
  • Pregnancy can increase Beta HCG levels. (Most home pregnancy tests involve measuring Beta HCG levels for this reason.)
  • Duodenal ulcers.
  • Cirrhosis of the liver.
  • Inflammatory bowel disease.

There is some preliminary work suggesting that vegetarians may have a higher false positive rate for beta HCG, and that this can be affected by consumption of vitamin B12. This study was with women only, not men, and may not necessarily apply to men.

False negatives in urine tests can be caused by drinking large amounts of fluids, taking diuretics, anti-convulsants, anti-parkinson drugs, tranquilizers, hypnotics or certain antihistamines (e.g., promethazine) before the test. Blood or protein in the urine can yield a false positive. The serum version of the test is generally not affected by these factors.

Bladder Tumor Antigen (BTA)

  • Infection of the genitourinary tract (e.g., urinary tract infection).
  • Recent bladder surgery.

CA 125

  • Endometriosis.
  • Pelvic Inflammatory Disease (PID).
  • Peritonitis
  • Ovarian cysts.
  • Fibroids
  • Ascites.
  • Cirrhosis of the liver.
  • Peritonitis.
  • Pleural effusion.
  • Pericardial effusion.
  • Pancreatitis.
  • Liver disease.
  • Menstruation.
  • Pregnancy.

CA 15-3

  • G-CSF chemotherapy.
  • Cirrhosis of the liver.
  • Benign breast disorders.

CA 19-9

  • Gallstones.
  • Acute cholangitis.
  • Pancreatitis.
  • Jaundice.
  • Biliary disease.
  • Ulcerative colitis.
  • Inflammatory Bowel Disease.
  • Cirrhosis of the liver.
  • Cholecystitis.

CA 27.29

  • Ovarian cysts.

Calcitonin

  • Pernicious anemia.
  • Thyroiditis.

CarcinoEmbryonic Antigen (CEA)

  • Inflammatory Bowel Disease.
  • Pancreatitis.
  • Liver disease.
  • Tobacco use can lead to elevated CEA levels. (CEA is elevated in 19% of smokers and only 3% of the non-smoking healthy population.)
  • Diverticulitis.
  • Hepatitis.
  • Peptic ulcers.
  • Hypothyroidism.
  • Cirrhosis of the liver.
  • COPD.
  • Lung infection.
  • Pleural effusions.
  • Biliary obstruction.
  • Treatment with oral 5-FU.
  • High serum glutamic-pyruvic transaminase (sGPT) levels.

Creatin-Kinase-CK

  • Renal failure.
  • Bowel infarction.
  • Stroke.

Lactate Dehydrogenase (LDH)

LDH is a generic indicator of tissue damage and is not specific to cancer. As such, it has a high false positive rate.

LDH values are primarily used in conjunction with other tumor markers for prognostic value and not as an indicator of relapse. There are no standard reference values for LDH, so LDH values should be compared with the reference values supplied by the laboratory. When other tumor markers show normal values, one generally should not be concerned about elevated LDH values unless the LDH values are more than 1.5 times the upper limit of normal and continue to increase in subsequent tests.

  • Heart failure (myocardial infarction) within the past two weeks.
  • Procainamides and other drugs used to treat arrhythmia.
  • Pulmonary infarction.
  • Stroke.
  • Hepatitis.
  • Hypothyroidism.
  • Anemia. (Hemolytic or pernicious anemia.)
  • Mono.
  • Lung disease.
  • Liver disease.
  • Kidney disease.
  • Pancreatitis.
  • Muscle trauma.
  • Muscular dystrophy.
  • Consumption of aspirin, narcotics or alcohol.
  • Recent anesthesia.

Fecal Occult Blood Test (FOBT)

  • Other sources of bleeding, such bleeding gums from dental work.
  • Anticoagulants and blood thinners like aspirin.
  • Steroids.
  • Iron.
  • Consumption of red meat within three days of the test.
  • Consumption of fish.
  • Consumption of turnips and horseradish.
  • Oxidizing drugs such as iodine and boric acid.
  • Colchicines.
  • Vitamin C consumption can cause false negatives.

NMP22

  • Recent surgery.
  • Chemotherapy.
  • Infection of genitourinary tract.
  • Bladder stones.
  • Kidney stones.

Placental Alkaline Phosphatase (PLAP)

  • Tests for placental alkaline phosphatase (PLAP) are significantly affected by smoking.

Prostate-Specific Antigen (PSA)

  • Benign Prostatic Hyperplasia (BPH).
  • Prostatitis.
  • Ejaculation within the previous 48 hours.
  • Recent prostate manipulation during a digital rectal exam (within the past six weeks).
  • Vigorous exercise affecting the prostate, such as bicycle riding.
  • African American men have higher than average PSA levels, and Asian men have lower than average PSA levels.
  • Older men are more likely to have false positives than younger men.
  • Chemotherapy involving cyclophosphamide and methotrexate.

Prostatic Acid Phosphatase (PAP)

  • Gaucher's disease.
  • Paget's disease.
  • Osteoporosis.
  • Cirrhosis of the liver.
  • Pulmonary embolism.
  • Hyperparathyroidism.


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