The Promise of Tumor Markers - page 3

Questions to Ask Your Doctor

If you have questions about tumor markers, be sure to ask your doctor, and keep asking until you understand. The following questions might help you plan your meeting with your doctor:

What tumor marker tests do you recommend for me? Which ones have you already performed?
How are these tests performed? How often should I have them?
Do I have abnormal levels of any tumor marker?
If I do have abnormal levels of a tumor marker, what does that mean? How will it affect my treatment?
How will you use tumor markers in my follow-up care? As with other laboratory tests, reliable tests for tumor markers must be both specific and sensitive.
If the test is not specific, there is a chance that the results could indicate a tumor marker is present when it is not (a false positive). In this case, a healthy person may go through unnecessary tests and anxiety.
If the test is not sensitive, the results may indicate a tumor marker is not present, when it actually is (a false negative). In this case, a person who may benefit from additional testing and treatment may not receive it.

Your doctor is the best person to talk to about testing for certain tumor markers.

CISN Summary

Tumor markers are recognized by most as a very promising tool that can achieve early diagnosis and more targeted treatments. Summarizing this in the broadest terms, many factors influence gene expression in the blood. See image below courtesy of Gene News

Heritable components derived from one's parents are one source of bloodbased gene expression.
External factors like air pollution or second hand cigarette smoke also generate gene expression changes in the body, which can be manifested in blood.
Internal factors such as a colon tumor for example also precipitate changes in gene expression in blood cells as they come in contact with the tumor and the body attempts to respond.

Blood is obtained by standard methods and RNA extracted from the blood in order to obtain a snapshot of specific gene expression changes that are direct and specific reflections of a disease state in the body. That "snapshot" is shown on the right as a molecular signature derived from microarray analysis (the disease snapshot and normal snapshot are clearly different).

Summary of 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 Mspike)	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	*Still under investigation	Age
membrane antigen (PSMA)
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

For More Information

Does the NCI have guidelines for the use of tumor markers?

No, the NCI does not have such guidelines. However, some organizations do have guidelines for some types of cancer.

The American Society of Clinical Oncology (ASCO), a nonprofit organization that represents more than 21,500 cancer professionals worldwide, has published clinical practice guidelines on a variety of topics, including tumor markers for breast and colorectal cancer. These guidelines, called Patient Guides, are available on the ASCO Web site at: http://www.plwc.org/.

The National Comprehensive Cancer Network® (NCCN), which is also a nonprofit organization, is an alliance of cancer centers. The NCCN provides Patient Guidelines, which include tumor marker information for several types of cancer. Most of the guidelines are available in English and Spanish versions. The Patient Guidelines are on the NCCN's Web site at: http://www.nccn.org/.

The National Academy of Clinical Biochemistry (NACB) is a professional organization dedicated to advancing the science and practice of clinical laboratory medicine through research, education, and professional development. The Academy publishes Practice Guidelines and Recommendations for Use of Tumor Markers in the Clinic, which focuses on the appropriate use of tumor markers for specific cancers. More information can be found on the NACB Web site at: http://www.aacc.org/.