Tumor marker

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Tumor markers are substances found in the blood, urine or body tissues that can be elevated in cancer. There are many different tumor markers. They are used in oncology to help determine the presence of cancer. An elevated level of a tumor marker can indicate cancer, however there can often also be other causes of the elevation.

Tumor markers can be produced directly by the tumor or by non-tumor cells as a response to the presence of a tumor.

Koepke^[1] outlines a hierarchy of clinical laboratory tests, from least to most informative. As used in oncology, they are as follows:

Screening for common cancers on a population basis

• Example: elevated prostate specific antigen suggests prostate cancer

Monitoring of cancer survivors after treatment

• Example: elevated AFP in a child previously treated for teratoma suggests relapse with endodermal sinus tumor

Diagnosis of specific tumor types, particularly in certain brain tumors and other instances where biopsy is not feasible

Tumor markers can be classified in two groups: Cancer-specific markers and tissue-specific markers.

Cancer-specific markers are related to the presence of certain cancerous tissue. Because there is a large overlap between the many different tumor tissue types and the markers produced these cancer tissue might not be specific in making a diagnosis. They can, however, be useful in the follow-up of treated patients to describe progress of the disease or response to treatment. A few examples of these markers are CEA, CA19-9, CA125.

An example of a cancer-specific marker, CEA, or carcinoembryonic antigen, is a blood-borne protein, first noted to be produced by tumors of the gastrointestinal system. Further investigation showed that it was produced by the occasional lung and breast cancer case, meaning that an elevated level does not mean a bowel cancer. However, in a patient with a history of a treated bowel cancer, a rising CEA level can be an early sign of bowel cancer return. This usually occurs before the site of return can be identified on imaging or examination and so many oncologists question the wisdom of doing a blood test for CEA when the end result is bad news that alarms the patient. Nevertheless, a sequence of steady low CEA readings can provide much needed reassurance to the post-operative patient. Also, a rising sequence of CEA readings should alert the physician to the need for diagnostic tests such as PET scans. +

Tissue-specific markers are related to specific tissues which have developed cancer. Generally speaking, these substances are not specifically related to the tumor, and may be present at elevated levels when no cancer is present. But unlike the previous group, elevated levels point to a specific tissue being at fault. Examples include PSA, beta-HCG - (Human chorionic gonadotropin), AFP - (Alpha-fetoprotein), AFP-L3 - (a lectin-reactive AFP) and Thyroglobulin. For example, if man has an elevated PSA, a search for prostate cancer will be undertaken. If an individual has an elevated level of beta-HCG, AFP or AFP-L3%, a search for a testicular or liver cancer, respectively, will be made.

• PSA (Prostate specific antigen) is produced by the normal prostate. It is a protein enzyme called a serine protease that usually acts as an anticoagulant to keep semen liquid. Only small amounts leak into the circulation in normal circumstances. Enlarged prostates leak more substantial amounts, and cancerous prostates also leak substantial amounts. An accurate way to tell if an elevated PSA level results from cancer is to biopsy the prostate.

• β-hCG: Elevated levels cannot prove the presence of a tumor, and low levels do not rule it out (an exception is in males who do not naturally produce β-hCG). Nevertheless, elevated βhCG levels fall after successful treatment (e.g. surgical intervention or chemotherapy), and a recurrence can often be detected by the finding of rising levels.

The hook effect (also known as high dose hook effect) is an artifact of tumor marker immunoassay kits, that causes the reported quantity of tumor marker to be incorrectly low when the quantity is high. An undetected hook effect may cause delayed recognition of a tumor.^[2] The hook effect can be detected by analyzing serial dilutions. Absent hook effect, reported quantities of tumor marker in a serial dilution should be proportional to the dilution.

If repeated measurements of tumor marker are needed, some clinical testing laboratories provide a special reporting mechanism, a serial monitor, that links test results and other data pertaining to the person being tested. This requires a unique identifier for the person. In the United States commonly a Social Security number is used for this. One important function of this mechanism is to ensure that each test is performed using the same assay kit. For example, for AFP many different commercial assay kits, based on different technologies, are available. AFP measurements obtained using different assay kits are not comparable unless special calculations are performed.

Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is an emerging field.^[1] In the United States, New York state is leading the way.^[3]

• Tumor antigen

• Tumor+Markers,+Biological at the US National Library of Medicine Medical Subject Headings (MeSH)

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