Tumor Markers

Tumor markers are substances that can often be detected in higher than normal amounts in the blood, urine, or body tissues of some patients with certain types of cancer. These substances can be proteins, enzymes, biochemicals, or antigens. Tumor markers may either be produced by the cancer itself or by the body in response to the cancer. In general, tumor marker levels are lower in early stage disease (but still higher than normal) and higher with advanced disease. Furthermore, their levels decrease in response to treatment and increase when the cancer progresses.

Tumor markers are often used to:

  • Monitor response to treatment—some tests show whether the cancer is responding to treatment
  • Monitor for progression—in general, an increase in some tumor markers indicates disease progression
  • Detect recurrence—regular monitoring of some tumor markers during a remission may help detect recurrence
  • Detect metastasis—metastasis is the spread of cancer from its site of origin to another distant location in the body
  • Screen at-risk individuals—Prostate specific antigen is an example of a tumor marker that is specific enough for one condition—prostate cancer—to function as a screening test for asymptomatic, at-risk men, which generally refers to men over 50 years of age with at least a 10-year life expectancy.
  • Identify specific cancer subtype—some cancers are divided into subtypes that are more or less aggressive; some tumor marker tests make it possible to distinguish between cancer types
  • Predict prognosis—test results may indicate the chance of a negative or positive outcome, based on outcomes of other patients with similar results

Tumor markers are not specific enough to be used alone for diagnosing cancer. There are several reasons for this:

  • Tumor marker levels can be elevated in people with benign (non-cancerous) disease.
  • Tumor markers are not elevated in every person with cancer, particularly those with early stage disease.
  • Most tumor markers are not totally specific for a single condition, meaning that many different cancers or diseases can result in a higher than normal level of a particular marker.

For these reasons, tumor markers are not used in isolation; instead, results from tumor marker tests are evaluated in the context of a patient’s history, symptoms, and other test results.

Despite these limitations, researchers continue to study the markers in table 1, as well as potential new markers to determine whether they may have a role in screening, early detection, and directing treatment.

Table 1: Tumor markers by cancer type

Tumor marker Primary use Other conditions that cause elevated levels Normal value

Detected in:

Bladder Cancer
Bladder tumor antigen (BTA) Detect recurrence
  • Recent surgery
  • Genitourinary tract infection
  • Cancer of kidney or ureters
Not detectable

urine

Nuclear matrix protein
(NMP 22)
Predict prognosis

Detect recurrence

  • Recent surgery
  • Chemotherapy
  • Genitourinary infection or disease
  • Renal or bladder stones
  • Rigorous exercise
<10 U/ml

urine

Breast Cancer
CA 15-3 Monitor response to treatment

Detect metastases

  • Cervical cancer
  • Liver cancer
<31 U/ml

blood

CA 27.29 Monitor response to treatment

Detect metastases

  • Cervical cancer
<38-40 U/ml

blood

Carcino-embryonic antigen
(CEA)
Predict prognosis

Monitor response to treatment

Detect recurrence

Used in combination with CA 15-3

  • Colorectal cancer
  • Lung cancer
  • Gastric cancer
  • Pancreatitis
  • Hepatitis
  • COPD
  • Cigarette smoking
<3 ng/ml

blood

Colorectal Cancer
Carcino-embryonic antigen
(CEA)
Predict prognosis

Detect recurrence

Monitor response to treatment

  • Breast cancer
  • Lung cancer
  • Gastric cancer
  • Pancreatitis
  • Hepatitis
  • COPD
  • Cigarette smoking
<3 ng/ml

blood

CA 19-9 Monitor response to treatment

Monitor progression

  • Pancreas cancer
  • Gastric cancer
  • Liver cancer
  • Pancreatitis
  • Ulcerative colitis
  • Inflammatory bowel disease
<33 U/ml

blood

Liver Cancer
Alpha-fetoprotein (AFP) Diagnose liver cancer in patients with chronic hepatitis

Follow-up after surgery for liver cancer

  • Germ cell cancer of ovaries/testes
  • Cirrhosis
  • Hepatitis
  • Inflammatory bowel disease
  • Pregnancy
0-6.4 IU/ml

blood

Lung Cancer (NSCLC)
Carcino-embryonic antigen
(CEA)
Diagnosis, but not very important because lung cancer can be easily seen on an x-ray
  • Colorectal cancer
  • Breast cancer
  • Gastric cancer
  • Pancreatitis
  • Hepatitis
  • COPD
  • Cigarette smoking
<3 ng/ml

blood

Lung Cancer (SCLC)
SCLC:

Neuron-specific enolase
(NSE)

Distinguish SCLC from NSCLC

Monitor response to treatment

Monitor progression

  • Neuroblastoma
  • Pancreatic cancer
  • Thyroid cancer
  • Chronic bronchitis
  • COPD
<13 ng/ml

blood

Lymphoma
Lactic dehydrogenase (LDH)
  • Hepatitis
  • Myocardial infarction
  • Melanoma metastasis
  • Liver metastases
100-210 u/l

blood

Beta-2-microglobulin (B2M) Predict prognosis

Monitor progression

  • Multiple myeloma
Gamma globulin
  • Multiple myeloma
3.0-13.0 g/L

blood

Melanoma Skin Cancer
TA 90 Detect metastasis

Predict prognosis

Not detected/

blood

Multiple Myeloma
Bence Jones protein Diagnosis

Predict prognosis

Monitor progression

Monitor response to treatment

  • Non-Hodgkin’s lymphoma
0.02 to 0.5 mg/mL

urine

Myeloma protein
(M-protein or M-spike)
Diagnosis

Predict prognosis

<30 g/L

blood

Beta-2-microglobulin (B2M) Predict prognosis

Monitor progression

  • Lymphoma
  • Acute lymphocytic leukemia
Gamma globulin
  • Non-Hodgkin’s lymphoma
3.0-13.0 g/L

blood

Ovarian Cancer (epithelial)
CA 125 Indicates most common form of ovarian cancer, epithelial

Monitor response to treatment

Detect recurrence

  • Breast cancer
  • Colorectal cancer
  • Ovarian cysts or fibroids
  • Endometriosis
  • Inflammatory bowel disease
  • Cirrhosis
  • Peritonitis
  • Pancreatitis
0-35 U/ml

blood

Ovarian Cancer (germ cell)
Alpha-fetoprotein (AFP) Diagnosis

Follow-up after treatment

  • Germ cell cancer of the testes
  • Cirrhosis
  • Hepatitis
  • Inflammatory bowel disease
  • Pregnancy
0-6.4 IU/ml

blood

Pancreatic Cancer
CA 19-9 Predict prognosis Monitor response to treatment

Monitor progression

  • Colorectal cancer
  • Gastric cancer
  • Liver cancer
  • Pancreatitis
  • Ulcerative colitis
  • Inflammatory bowel disease
<37 U/ml

blood

Prostate Cancer
Prostate specific antigen (PSA) Screening

Detect early stage disease

Monitor progression

<4 ng/ml

blood

Prostatic acid phosphatase (PAP) *Rarely used because PSA is more sensitive
  • Present in many body tissues
  • Enlarged prostate
Varies from lab to lab

blood

Prostate-specific membrane antigen (PSMA) *Still under investigation
  • Age
Testicular Cancer
Human chorionic gonadotropin (hCG) Diagnose at-risk individuals

Monitor response to treatment

Detect metastases

  • Pregnancy
  • Cirrhosis
  • Duodenal ulcers
  • Benign breast, lung, pancreas, ovary, GI cancers
  • Choriocarcinoma
  • Mediastinal germ cell neoplasms
>31 ng/mL

blood

Alpha-fetoprotein (AFP) Diagnose

Follow-up after treatment

  • Germ cell cancer of the ovaries
  • Cirrhosis
  • Hepatitis
  • Inflammatory bowel disease
  • Pregnancy
<40 ng/mL

blood

Thyroid Cancer
Calcitonin Diagnose early disease

Screening for at-risk individuals

  • Lung cancer
    (rarely measured)
<13 pg/ml

blood

Thyroglobulin Monitor response to treatment

Monitor progression

>1 µg/L

blood

New advances in tumor marker tests: Most tumor markers are proteins. Since DNA is the code that determines which proteins will be produced by a cell, researchers are developing methods to detect DNA. Even in many early stage diseases, cancer cells may break away from the tissue where they originated and can be detected in the blood or other body substances. For example, researchers have detected abnormal DNA in the:

  • Blood of people with breast, liver, lung, ovarian cancer, and melanoma
  • Urine of individuals with bladder cancer
  • Saliva of individuals with cancers of the oral cavity

This new approach to tumor marker testing can be thought of as measuring the cause (DNA) rather than the effect (protein), and may thus provide even more accurate and useful information for screening, early detection, monitoring, and planning treatment.

Researchers from Italy have found that measuring circulating DNA appears to be an accurate and quick method of detecting lung cancer, even in its earliest stages. This trial involved 100 patients who had been newly diagnosed with lung cancer, with stages I – IV (earliest stage to most advanced stage). Blood was drawn and tested for DNA in 100 patients who had been newly diagnosed with lung cancer (stages I-IV) and compared blood drawn from control groups, which included:

  • Individuals who were heavy smokers but did not have lung cancer, and
  • Individuals who were not smokers and did not have lung cancer.

DNA levels in the blood were 8 times higher in patients with lung cancer, compared to the control group. These levels were also detected in individuals with early-stage cancer. Only patients with cancer had high levels of DNA in their blood. Elevated DNA accurately detected lung cancer in 90% of cases.[1]

References

[1] Sozzi G, Conte D, Leon M, et al. Quantification of free circulating DNA as a diagnostic marker in lung cancer. Journal of Clinical Oncology 2003;21:3902-3908.