Patient Guide to Tumor Markers

Carolyn Vachani RN, MSN, AOCN
The Abramson Cancer Center of the University of Pennsylvania
Last Reviewed: March 5, 2018

Key Takeaways:

  • Tumor markers are substances that may be elevated when there is cancer in the body.
  • They are not very “specific”, meaning non-cancer health issues can also cause them to be elevated.
  • They must be used along with radiology tests and exams by your healthcare provider.

 

What is a tumor marker?

A tumor marker is a substance that is made by the body because a cancer is present. Or it can be made by the cancer itself. Some of these markers are specific to one cancer. Some are seen in several types of cancer. The markers can be found in the blood, urine or tissues.

What are tumor markers used for?

Tumor markers are most often used to track how a patient's cancer responds to treatment. If the level is going down, the treatment is working. If it goes up, the cancer may be growing. There are health issues that can cause markers to be elevated that are not cancer. Because of this, you must think about the tumor marker levels along with the results of radiology scans (CT scan, MRI, Ultrasound), the patient’s symptoms, and the healthcare provider’s exam.

In some cancers, markers are used to watch for recurrence (return of the cancer after treatment). This is not useful in all cancer types. In breast cancer, research has found that watching tumor markers after treatment does not help people live longer. For that reason they are not recommended.

Tumor markers can also be used along with other tests (scans, biopsies, and so on) to help find cancer in a patient who has symptoms that are suspicious for cancer. Some markers can help healthcare providers to predict how the patient will do and to decide on treatment.

Can a tumor marker be used to screen for cancer?

Ideally, markers could be used as a screening test (looking for a cancer in people who do not have symptoms) for the general public. The goal of a screening test is to find 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 approval as a screening tool is the Prostate Specific Antigen (PSA) for prostate cancer, though this has concerns as well.

The main worry with tumor markers is that they are not specific enough – they have too many false positives. This means that the level is elevated, when no cancer is present. This leads to costly tests that are not needed and causes the patient to be worried. The other concern is that the marker is not elevated early enough in the life of the cancer, and so the cancer cannot be found any earlier then when symptoms start to appear. Keep in mind that some substances used as tumor markers are normally made in the body, and a "normal" level is not always zero.

Does every cancer type have a tumor marker?

There is not a known tumor marker for all types of cancer. Also, tumor markers are not raised in all cases of the cancers they are used for, so they are not helpful for all patients. For example, carcinoembryonic antigen (CEA) is a tumor marker used in colon cancer, yet only 70-80% of colon cancers make CEA. This means 20-30% of people with colon cancer will not have a raised CEA level. Only 25% of early stage colon cancers have a raised CEA. Because of this, CEA cannot always help find colon cancer in its early stages, when cure rates are best.

The bottom line is, tumor markers can be very helpful in watching a person's response to treatment and, in some cases, watching for the cancer to return. However, they need to be used along with your healthcare provider’s exam, talking about any symptoms you are having, and radiology studies (CT scan, MRI, PET, and so on).

Guide to Tumor Markers Used in Cancer

This is a table of the most often used tumor markers, the cancers they can be found with, non-cancerous health issues that can cause them to be elevated, and the range of normal results.

In cases where the half-life is listed, this should be kept in mind 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 raised. If the level were checked a week later, the result should be zero, or very close to zero, if no prostate cells remain.

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

Cytokeratin Fragment 21-1
(Blood Test)

Lung, urologic, gastrointestinal, and gynecologic cancers

Lung disease

0.05-2.90 ng/ml

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.

National Cancer Institute. Tumor Markers. 2015. Found at: http://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-fact-sheet.

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.

Blogs

How to Say the Wrong Thing
by OncoLink Team
April 18, 2018

Farewell Lil’e!
by OncoLink Team
April 6, 2018

A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
R
S
T
U
V
X
Y
Z
#
 
A
B
C
E
G
H
K
L
M
N
O
P
R
S
T
U
 
 
 
 
Stay informed with the latest information from OncoLink!   Subscribe to OncoLink eNews
View our newsletter archives