Alpha-fetoprotein|Progesterone| hCG |Oestrogens|Oestrogen receptor|BRCA|CEA|CA-125|CA 15-3|CA 19-9|PSA|Thyroglobulin|Calcitonin
What are they?
Tumour markers are substances, usually proteins, produced by the body in response to cancer growth or produced by the cancer tissue itself. Some markers are specific to a particular type of cancer, while others are non-specific because they are found in many forms of cancer. Many of the best-known markers are found not only in cancers but also in a variety of other non-cancerous conditions. Consequently, tumour markers cannot be used to diagnose cancer.
Only a few well-known markers are used in routine clinical practice. Many other potential markers are still being studied. In general, when new markers are discovered, they raise great hopes, but after further research they turn out to be no more useful than the markers already in use.
The goal is to detect and diagnose cancers early, when treatment can still be effective and before the tumour has had a chance to grow and spread. So far, however, no marker has been approved for screening people without symptoms, including prostate-specific antigen (PSA). The markers are either not specific enough (too many false positives, leading to expensive and unnecessary further tests) or are not raised at a sufficiently early stage of the disease. In 1968 the World Health Organization proposed ten recommendations to follow when promoting national screening programmes. These recommendations stress that the disease to be screened for must be important, well understood, recognisable and detectable early. Medical advice and treatment must be available and more effective if offered in the early stages of the disease. The health benefits obtained must outweigh any harm caused by the screening tests, which must be cost-effective.
Some people are at high risk of developing cancer because they carry a genetic mutation. Although they are not considered tumour markers, there are tests that can identify these mutations in order to estimate the risk of developing a certain type of cancer. BRCA1 and BRCA2 are examples of gene mutations linked to the risk of developing inherited breast and ovarian cancer.
Why are they done?
Tumour markers are not diagnostic in themselves. A definite diagnosis of cancer is made by histological examination of a sample (for example tissue) obtained by biopsy. However, tumour markers provide useful information for:
Screening in “at-risk” families. At present no markers are available for mass screening, although some can be used to follow people with a strong family history of a particular type of cancer. Genetic markers can be used to stratify risk in family members.
Diagnosis. In a patient with symptoms, the marker can help identify the origin of the cancer, for example CA-125 for ovarian cancer, or distinguish it from other conditions. It is important to remember that the marker does not diagnose cancer, but provides valuable support in the diagnostic process.
Staging. When cancer is present, tumour marker levels can provide information on its spread to other organs and tissues. Prognosis. The marker can help assess how aggressive the cancer is.
Choice of treatment. Some markers, such as Her2/neu, provide information on the type of treatment the cancer is most likely to respond to (for example, Her2/neu-positive breast cancers are more likely to respond to treatment with trastuzumab (Herceptin)).
Monitoring treatment. Markers are useful for monitoring the effectiveness of treatment, especially in more advanced forms. If marker levels fall, the treatment is working; if they remain high, treatment needs to be adjusted. However, the information obtained must be assessed carefully. CEA, for example, is measured to monitor bowel cancer, but not all bowel cancers have high CEA levels. If a marker’s levels are not raised when the cancer is diagnosed, it cannot be used to monitor subsequent treatment.
Detecting recurrence. One of the most important uses of markers at present is monitoring for recurrence. If a marker is high before treatment, low after treatment and then rises progressively, the cancer has probably come back. (If, on the other hand, marker levels remain high after surgery, it is likely that not all the tumour tissue was removed during the operation.)
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