A tumor marker is a biomarker found in blood, urine, or body tissues that can be elevated by the presence of one or more types of cancer. There are many different tumor markers, each indicative of a particular disease process, and they are used in oncology to help detect the presence of cancer. An elevated level of a tumor marker can indicate cancer; however, there can also be other causes of the elevation (false positive values).
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Tumor markers can be produced directly by the tumor or by non-tumor cells as a response to the presence of a tumor.
Although mammography, ultrasonography, computed tomography, magnetic resonance imaging scans, and tumor marker assays help in the staging and treatment of the cancer, they are usually not definitive diagnostic tests. The diagnosis is mostly confirmed by biopsy.
Classification
On the basis of their chemical nature tumor markers can be proteins, conjugated proteins, peptides or carbohydrates. Proteins or conjugated proteins may be enzymes, hormones or fragments of proteins. Sequencing of genes for diagnostic purposes is mostly classified under the biomarker heading and is not treated here.
Uses
Tumor markers may be used for the following purposes:
As stated in the BMJ 2009, tumor markers should not generally be used for the purpose of diagnosis of cancers, as opposed to monitoring purposes in certain cancers, or in certain cases, for screening purposes. The use of these tests without understanding their utility has resulted in inappropriate use of tumor marker blood tests, which has resulted in inappropriate over-investigation for cancers.
Techniques
Tumor markers can be determined in serum or rarely in urine or other body fluids, often by immunoassay but other techniques such as enzyme activity determination are sometimes used. Microscopic visualization in tissue by immunohistochemistry does not give quantitative results and is not considered here.
For many assays, different assay techniques are available. For monitoring it is important that the same assay is used as the results from different assays are generally not comparable. For example, for AFP many different commercial assay kits, based on different technologies, are available and for thymidine kinase there are assays for either enzyme activity or amount of substance.
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 & Civil Personal Record (CPR) in Bahrain are used for this.
Interlaboratory proficiency testing for tumor marker tests, and for clinical tests more generally, is routine in Europe and an emerging field. in the United States. New York state is prominent in advocating such research.
Precision and accuracy
The required precision and accuracy for different analytes varies: some analytes give small or moderate changes in concentration or activity, thereby requiring high accuracy and precision to be useful while others that show large differences between normal and pathological values may be useful even if the precision and accuracy are inferior. Therefore, the required precision and accuracy for a given assay may be different for different applications such as in different diagnoses or for different uses. This also influences the useful working range for a given assay for different diagnosis or uses. Every laboratory should verify the precision and accuracy of the assays with the instruments and personnel used.
The high dose hook effect is an artifact of immunoassay kits, that causes the reported quantity to be incorrectly low when the quantity is high. An undetected hook effect may cause delayed recognition of a tumor. The hook effect can be detected by analyzing serial dilutions. The hook effect is absent if the reported quantities of tumor marker in a serial dilution are proportional to the dilution.
Multiple Tumor marker test
As with other diagnostic tests, tumor markers have a few test characteristics that influence their usability:
As with other tests, predictive value (the chance that a positive or negative result represents the truth), depends strongly on the pre-test probability. The predictive value may be increased if two or more tests are carried out in parallel. The condition is that the tests have in themselves similar predictive values.
Test combinations that will give more exact results are for instance: