Patient Guide to Tumor Markers

Carolyn Vachani RN, MSN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: August 6, 2013

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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 some acceptance as a screening tool is the Prostate Specific Antigen (PSA) for prostate cancer, though this has its share of controversy. Other markers are either not specific enough (too many false positives - a positive result, when no cancer is actually present - leading to expensive, anxiety producing 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 with, 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 Reasons for Elevated Levels

"Normal" Results

Blood test (blood serum marker), except where noted.

(**) indicates the most common association, if one exists

 

Different labs may have different high/low values

 AFP
Alpha-fetoprotein

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)

Bence-Jones Proteins
(urine test)
or
Monoclonal Immunoglobulins (blood test)

Multiple Myeloma** Waldenstrom's macroglobulinemia, chronic lymphocytic leukemia

Amyloidosis

Generally, a value of 0.03-0.05 mg/ml is significant for early disease

B2M
Beta-2-Microglobulin

Multiple myeloma**, chronic lymphocytic leukemia (CLL), and some lymphomas (including Waldenstrom’s macroglobulinemia)

Kidney disease, hepatitis

< 2.5 mg/L

BTA
Bladder Tumor Antigen
(urine test)

Bladder cancer**,
cancer of kidney or ureters

Invasive procedure or infection of bladder or urinary tract

None normally detected

CA 15-3
Cancer Antigen 15-3 or Carbohydrate Antigen 15-3

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
Cancer Antigen 19-9 or Carbohydrate Antigen 19-9

Pancreas** and colorectal, liver, stomach and biliary tree cancers

Pancreatitis, ulcerative colitis, inflammatory bowel disease, inflammation or blockage of the bile duct, thyroid disease, rheumatic arthritis

< 37 U/ml is normal
> 120 U/ml is generally caused by tumor

CA 125
Cancer Antigen 125 or Carbohydrate Antigen 125

Ovarian cancer** breast, colorectal, uterine, cervical, pancreas, liver, lung

Pregnancy, menstruation, endometriosis, ovarian cysts, fibroids, pelvic inflammatory disease, pancreatitis, cirrhosis, hepatitis,  peritonitis, pleural effusion, following surgery or paracentesis

0-35 U/ml

CA 27.29
Cancer Antigen 27.29 or Carbohydrate Antigen 27.29

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)

Calcitonin

Medullary thyroid cancer**

Chronic renal insufficiency, Chronic use of Proton-pump inhibitors (medications given to reduce stomach acid)

<8.5 pg/mL for men
< 5.0 pg/mL for women

CEA
Carcinoembryonic Antigen

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

Chromogranin A

Neuroendocrine Tumors**, carcinoid tumors, neuroblastoma, and small cell lung cancer

Proton-pump inhibitors (medications given to reduce stomach acid)

Normal varies on how tested, but typically < 39 ng/l is normal

HCG
Human Chorionic Gonadotrophin
Or Beta-HCG, B-HCG

Germ cell, testicular cancers**, gestational trophoblastic neoplasia

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

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

LDH
Lactic Dehydrogenase

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

NSE
Neuron-specific Enolase

Small cell lung cancer**, neuroblastoma

Proton pump inhibitor treatment, hemolytic anemia, hepatic failure, end stage renal failure, brain injury, seizure, stroke

Normal < 9 ug/L

NMP 22
(urine test)

Bladder cancer**

BPH (benign prostatic hypertrophy), prostatitis

Normal < 10 U/ml

PAP
Prostatic Acid Phosphatase

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/ inflammation, ejaculation

Normal < 4 ng/ml (half life 2-3 days)

Tg
Thyroglobulin

Thyroid Cancer

Anti-thyroglobulin antibodies

< 33 ng/mL; if entire thyroid removed
< 2 ng/mL

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. 

Duffy MJ. Tumor markers in clinical practice: a review focusing on common solid cancers. Med Princ Pract. 2013;22(1):4-11. 

Febbo PG, Ladanyi M, Aldape KD, De Marzo AM, Hammond ME, Hayes DF, Iafrate AJ, Kelley RK, Marcucci G, Ogino S, Pao W, Sgroi DC, Birkeland ML. NCCN Task Force report: Evaluating the clinical utility of tumor markers in oncology. J Natl Compr Canc Netw. 2011 Nov;9 Suppl 5:S1-32; quiz S33.

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. 

Sturgeon, CM, Lai LC, Duffy MJ. Serum tumour markers: how to order and interpret them. BMJ. 2009; 339:852-858 

Vaidyanathan K, Vasudevan DM. Organ Specific Tumor Markers: What's New? Indian J Clin Biochem. 2012;27(2):110-20.