What are Tumor Markers with Cancer?

Common biomarkers used to monitor, diagnose, screen for, or stage cancer

cancer cells under the microscope may correlate with tumor marker levels
Microscopic sample of one type of lung cancer (squamous cell carcinoma). National Cancer Institute

Tumor markers are substances that are released by cancer cells or produced by the body in reaction to a malignant tumor or benign condition. By measuring these biomarkers in blood, urine, or other fluids, they may be used to monitor the progress of a cancer, check for recurrence, or sometimes to help screen for, diagnose, and/or stage cancer. Tumor marker results aren't usually used alone, but can provide clues when combined with clinical symptoms, imaging studies, and more. Most tumor markers are proteins such as CEA, CA-125, and PSA, but DNA changes such as mutations and other alterations may also be used as biomarkers or tumor markers.

Purpose of Tests

There are a number of reasons why a tumor marker test may be ordered:

  • To monitor progress of a cancer: The most common use of tumor markers is to follow a known cancer. In this setting, a decrease in the level of a tumor marker may be a sign that a tumor is decreasing in size (in other words, that the treatment is working) whereas an increase in the level could mean a tumor is progressing.
  • To monitor for cancer recurrence: With some cancers such as colon cancer, an increase in a particular tumor marker may indicate a recurrence of the cancer after surgery (curative treatment).
  • To help diagnose cancer: Tumor markers are not used alone to diagnose cancer, but may provide clues as part of the workup.
  • To screen for cancer: An example of a tumor marker used for screening is the PSA test for prostate cancer. (PSA can be used as both a screening test and to monitor a cancer). In some cases, a tumor marker may be used to to screen people who have a high risk of developing a particular cancer (but not the general population).
  • To help stage a tumor: In some cases, tumor markers may be helpful in determining the stage of a cancer (and properly determining stage is often extremely important in choosing the best treatment options).
  • To help diagnose metastases: If a particular tumor marker level is very high, it may suggest that a tumor is not only growing, but has spread (metastasized) to other regions of the body.
  • To estimate prognosis: In some cases, higher levels of a particular tumor marker may indicate a poorer prognosis.
  • To determine treatment choice: Gene mutations and other genomic alterations may be used to determine if targeted therapy is indicated, to learn if resistance to targeted therapy has developed, to predict prognosis, and hopefully, as screening tests in the future. Examples include EGFR testing in lung cancer and oncotype testing in breast cancer. When genetic biomarkers are used to determine treatment, it is referred to as precision medicine.
  • To predict complications of cancer: A 2018 study found that high tumor markers (CEA, CA 19-9, and CA 125) in people with colon, pancreatic, and ovarian cancers were associated with a high risk of blood clots (deep vein thrombosis), a complication which already affects roughly 20% of people with cancer at some time.
  • In clinical trials: The level of a tumor marker may be used to give objective information as part of a clinical trial.

Tumor Marker Basics

Some tumor markers may be increased in one type of cancer while others may be increased in several types. Even when a tumor marker is associated with a particular cancer, however, negative levels do not necessarily mean the cancer isn't present or is improving, and positive levels don't necessarily mean a cancer is present or worsening.

While there are several reasons why a tumor marker may be tested, these tests are often most valuable when repeated (serial measurements) to look at the progress of a tumor over time.

Measurement

With protein tumor markers, tests are most often done on blood, but may also be performed on urine, stool, cerebrospinal fluid, peritoneal fluid (abdominal fluid), or pleural fluid in some cases. With genetic biomarkers, tests may be done on tumor tissues or via a blood test that looks for circulating tumor cell DNA (liquid biopsy).

The "normal" range of several common tumor markers is discussed below.

With many tumor markers, some of the protein will be found in the blood or other fluids. This is because normal cells make many of these substances, but they may be produced in much higher amounts by cancer cells (or in response to cancer cells). When tumor markers are present in higher amounts, physicians refer to the marker as being "overexpressed."

Limitations

There are a number of limitations in using tumor markers to monitor cancer. Some of these include:

  • Absence of tumor markers for some cancers: Some cancers do not produce or result in the production of any tumor markers.
  • False negatives: In some cancers, particularly early-stage cancers, tumor markers may not be elevated. For example, carcinoembryonic antigen (CEA) elevations are present in a large number of people with advanced colon cancer, but increases are much less common with early stage disease.
  • False positives: With some tumor markers, there are a number of benign conditions that can cause increases as well. For example, CA-125 may be increased with ovarian cancer, but also with uterine fibroids, pregnancy, liver disease, and more.
  • Timing: The level of a tumor marker at one point in time may not necessarily reflect the status of the cancer. For example, if a tumor is responding to treatment it may take time for tumor marker levels to decrease, and if a lot of cancer cells are dying, levels may even increase for a period of time.

Similar Tests

Some tumor marker tests overlap significantly such that both tests are not usually recommended. An example is that of CA 27.29 and CA15-3 when used to monitor breast cancer.

Complementary Tests

Tumor markers should always be used along with other findings (such as symptoms or imaging studies) to evaluate the progress of a cancer.

Risks and Contraindications

The risk of tumor marker tests are primarily that of the procedure used to obtain fluid or tissue to test, whether a blood draw, thoracentesis to obtain pleural fluid, or biopsy to obtain a tissue sample.

If used without considering other findings, tumor markers could theoretically provide inaccurate information (either false positives or false negatives) leading to less than optimal treatment.

Interpreting Results

How to interpret the results of a tumor marker will depend on the specific tumor marker and setting in which it is used. The following graph lists some tumor markers followed by a brief discussion of common conventional (protein) and genetic biomarkers.

Common Tumor Markers
Tumor Marker Cancer Types Use with Cancer Other Conditions That Cause Elevations Normal Values
Alpha fetoprotein (AFP) Liver cancer
Germ cell tumors of ovary and testes
Diagnosis
Treatment monitoring
Staging
Recurrence Prognosis
Uterine fibroids
Pregnancy
Pancreatitis
0 to 6.4 IU/ml
Bence Jones protein Myeloma Diagnosis
Treatment
  None detected
Beta-2-microglobulin (B2M) Myeloma
Chronic lymphocytic leukemia
Some lymphomas
Guide treatment
Monitor treatment
Recurrence
Prognosis
Kidney disease  
Beta human chorionic gonadotropin
(beta-hCG)
Choriocarcinoma
Germ cell tumors of the ovary or testes
Staging
Prognosis
Treatment
Pregnancy
Marijuana use
Less than 31 IU/ml
Bladder tumor antigen (BTA) Bladder cancer Detect recurrence Kidney cancer
Urinary tract procedures or infections
 
Cancer antigen 15-3
(CA 15-3)
Breast cancer Monitor treatment
Detect recurrence
  Less than 31 U/ml
Cancer antigen 27.29
(CA 27.29)
Breast cancer same as CA 15-3   Less than 38 to 40 U/ml
Cancer antigen 19-9
(CA 19-9)
Pancreatic cancer, gallbladder, bile duct, stomach, and colon cancers Monitor for recurrence Bile duct obstruction
Thyroid disease
Inflammatory bowel disease
Pancreatitis
Less than 33 U/ml
Cancer antigen 125
(CA 125)
Ovarian cancer and peritoneal cancer, also uterine, liver, cervical, pancreatic, colon, and breast cancers   Uterine fibroids, pregnancy, liver disease 0 to 35
Calcitonin Medullary thyroid cancer     Less than 0.155 mg/ml (women)
Less than 0.105 ng/ml (female)
Calretinin Mesothelioma, germ cell tumors, synovial sarcoma, adrenocortical carcinoma      
Carcinoembryonic antigen (CEA) Colorectal cancer, also lung, breast, ovarian Check for recurrence, spread
Staging
Progression
  Less than 3 ng/ml (nonsmokers)
Less than 5 ng/ml (smokers)
Chromogranin-A Neuroblastoma
Pheochromocytoma
APUDoma
VIPoma
Diagnosis
Monitor treatment
Check for recurrence
   
CK Breast, ovary, colon, prostate cancers   Kidney failure 40-200 U/l (male)
35-150 U/l (female)
5-HIAA Malignant carcinoid tumors, stomach, appendix, colon cancer      
Lactate dehydrogenase (LDH) Testiular cancer, germ cell tumors, Ewing sarcoma, leukemias, lymphomas, myeloma, neuroblastoma Staging
TreatmentRecurrence
Heart attack, heart failure, hypothyroidism, anemia, liver disease, manu other cancers 100-210 U/l
NSE Neuroblastoma
Small cell lung cancer
    Less than 13 ng/ml
Nuclear matrix protein 22 (NMP 22)       Less than 10 U/ml
Prostatic acid phosphatase (PAP) Prostate cancer, also may be increased with testicular cancer, non-Hodgkin lymphoma, leukemia     0.5-1.9 U/l
PSA Prostate cancer Screening, monitoring, test for recurrence Benign prostatic hypertrophy (BPH) Less than 4 mg/ml
Urine catecholamines (VMA and HVA) Neuroblastoma, pheochromocytoma, PNET, rhabdomyosarcoma     8-35 mmols/24 hours (urine)
Thyroglobulin Thyroid cancer     Less than 33 mg/ml

Conventional Tumor Markers

Some of the more common (mostly protein) tumor markers include:

Carcinoembryonic Antigen (CEA):

Carcinoembryonic Antigen (CEA) may be used to look for recurrence, spread, or progression of colorectal cancer. It is also used with some other cancers.

CA 15-3 and CA 27.29

Either CA-15.3 or CA 27.29 may be checked to monitor for recurrence or progression of breast cancer, stomach cancer, colon cancer, lung cancer, and others. False positives are common, and levels can be elevated with a number of benign breast conditions. Since the two markers give similar results, only one of the tests is usually ordered.

CA 19-9

CA 19-9 may be checked to monitor treatment or screen for recurrence of pancreatic, gallbladder, bile duct, stomach, or colon cancer. False positives may occur with bile duct obstruction, thyroid disease, inflammatory bowel disease, and more.

CA 125

CA 125 may be used to monitor progress with ovarian cancer. While it has sometimes been used to screen for the disease, there are many false positives.

Alpha-Fetoprotein (AFP)

AFP may be used to test for recurrence, help diagnose, or monitor treatment with liver cancer and germ cell tumors of ovary or testicles. False positives may occur with uterine fibroids, pregnancy, pancreatitis, and more.

AFP is also helpful in the diagnosis of testicular cancer as it can help distinguish seminomas from non-seminomas.

PSA

PSA has been widely used to screen for prostate cancer, though the risk of overdiagnosis has called this in to question. It is still used to monitor response to treatment.

Calcitonin

Calcitonin is used to monitor medullary thyroid cancer.

Beta-human-chorionic gonadotropin (Beta hCG)

Beta hCG, known more widely as the test used to confirm pregnancy, is used to monitor choriocarcinoma and germ cell tumors. It may be elevated in both seminoma and non-seminoma testicular cancers. (It is hCG that is responsible for one of the symptoms of testicular cancer in men, gynecomastia, or breast enlargement.)

Gastrin

Gastrin is a tumor marker that may be found with gastrinomas, and may be helpful in diagnosis, treatment, and predicting recurrence. False positive results may occur with Zollinger Ellison syndrome.

Thyroglobulin

Thyroglobulin is used to monitor some types of thyroid cancer.

Neuron-Specific Enolase (NSE)

NSE may be used to monitor neuroblastoma as well as small cell lung cancer.

Beta-2-Microglobulin (B2M)

B2M may be used to monitor treatment, check for recurrence, and estimate prognosis for some leukemias, lymphomas, and myelomas. False negatives may occur with kidney disease.

Estrogen and Progesterone Receptors

ER and PG receptor studies are done with breast cancer to determine who is a candidate for hormonal therapy.

LDH

Lactic dehydrogenase or LDH is a very nonspecific tumor marker test that may be ordered during the work-up or management of many cancers. Levels tend to increase when a cancer is progressing or has metastasized, but there are many other non-cancerous conditions that can cause elevations as well, such as autoimmune conditions, heart disease, and many infections.

CD Markers

CD markers, referring to "cluster differentiation" markers, are proteins found on the surface of lymphoma cells.

T lymphocytes (T cells) and B lymphocytes (B cells) can look identical under the microscope. The CD20 tumor markers is used to distinguish between lymphomas made up of B cells or T cells.

These markers can help in the diagnosis, guide treatment (some medications target these specific proteins), or help predict prognosis.

Programmed death ligand 1 (PD-L1)

PD-L1 levels can help determine who is most likely to respond to the immuntherapy drugs called checkpoint inhibitors, though some people with low levels will also respond.

Others

There are many other tumor markers that are used less frequently, such as to distinguish uncommon types of pancreatic cancer, mesothelioma, and other tumors.

DNA Changes and Gene Expression Patterns

Genetic biomarkers may be done to see if targeted therapies are indicated, to determine if chemotherapy should be given after surgery for breast cancer, and sometimes to estimate prognosis. They may also be checked to look for evidence of hereditary cancer The tests may be done on tissue samples, or via a blood test (liquid biopsy) looking for cell free DNA from tumor cells.

Examples include:

  • EGFR mutations, ALK rearrangements, ROS1 rearrangements in lung cancer: The presence of genetic alterations may indicate the tumor will respond to a currently approved targeted therapy.
  • HER2 expression in breast cancer (and some lung cancers): People who have tumors with increased HER2 expression may respond to HER2 targeted therapies.
  • BRAF mutations in melanoma and lung cancer
  • Philadelphia chromosome (BCR-ABL fusion gene): The presence of this fusion gene may help in diagnosis, monitoring treatment, and checking for recurrence.
  • BRCA mutations and other mutations associated with breast cancer such as PALB2: When mutations are found that raise breast cancer risk, people who harbor these mutations are referred to as "previvors."
  • Oncotype testing 21 or 70: These profiles may help estimate the risk of recurrence and thus determine who should have chemotherapy after surgery for breast cancer.
Was this page helpful?

Article Sources

Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial policy to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.