Tumour markers

Published on 01/03/2015 by admin

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Tumour markers

A tumour marker is any substance that can be related to the presence or progress of a tumour. In practice, the clinical biochemistry laboratory measures markers that are present in blood, although the term ‘tumour markers’ can also be applied to substances found on the surface of, or within, cells fixed in frozen or paraffin sections. A tumour marker in plasma has been secreted or released by the tumour cells. Such markers are not necessarily unique products of the malignant cells, but may simply be expressed by the tumour in a greater amount than by normal cells.

Tumour markers fall into one of several groups: they may be hormones, e.g. human chorionic gonadotrophin (HCG) secreted by choriocarcinoma; or enzymes, e.g. prostate specific antigen (PSA) in prostate carcinoma; or tumour antigens, e.g. carcinoembryonic antigen (CEA) in colorectal carcinoma.

The use of tumour markers

Tumour markers can be used in different ways. They are of most value in monitoring treatment and assessing follow-up (Fig 70.1), but are also used in diagnosis, prognosis and screening for the presence of disease.

Fig 70.1 The use of tumour markers.

Monitoring treatment

Treatment monitoring is the area in which most tumour markers have found a useful role. The decline in concentration of the tumour marker is an indication of the success of the treatment, whether that be surgery, chemotherapy, radiotherapy, or a combination of these. However, the rate of decline of marker concentration should match that predicted from knowledge of the marker’s half-life. A slower than expected fall may well indicate that not all the tumour has been eliminated.

Assessing follow-up

Even when a patient has had successful treatment, it is often valuable to continue to monitor the marker long after the levels have appeared to stabilize. An increase indicates recurrence of the malignancy. Detection of increasing marker concentration allows second-line therapy to be instituted promptly. The frequency of sampling, with the attendant cost implications, is much discussed.

Diagnosis

Markers alone are rarely used to establish a diagnosis. Their detection in blood when there is clinical evidence of the tumour as well as radiological and, perhaps, biopsy evidence, will often confirm the diagnosis.

Prognosis

To be of value in prognosis, the concentration of the tumour marker in plasma should correlate with tumour mass. For example, HCG correlates well with the tumour mass in choriocarcinoma, HCG and alpha-fetoprotein (AFP) correlate with the tumour mass in testicular teratoma, and paraproteins correlate with the tumour mass in multiple myeloma.

Screening for the presence of disease

In routine clinical practice tumour markers should not be used to screen for malignancy, however appealing this might be in theory.

The exception to this rule is the screening of specific high-risk populations. For example, the hormone calcitonin, which is increased in all patients with medullary carcinoma of thyroid, may be used to screen close relatives. Prophylactic thyroidectomy may then be advised if any are found to have elevated calcitonin concentrations.

A practical application of tumour markers

Some of the uses of tumour markers discussed above can be illustrated with reference to Figure 70.2. This shows how the tumour marker AFP was helpful in the management of a young man with a malignant teratoma. The presence of AFP together with the hormone HCG confirmed the diagnosis. Between 75 and 95% of all patients presenting with testicular teratoma have abnormalities in one or both of these markers. The very high concentration of AFP (>10 000 kU/L) indicated that the prognosis was not good, and that it was likely there would be tumour recurrence after treatment. In fact, AFP concentrations fell in response to chemotherapy, and when the levels reached a plateau, surgery was carried out. Thereafter, chemotherapy was continued, and AFP fell to very low levels. Continued monitoring of AFP levels in such a patient would provide early warning of tumour recurrence.

Fig 70.2 The use of AFP measurements in the management of a patient with a testicular teratoma.

Tumour markers with established clinical value

Markers play a major role in the management of germ cell tumours and choriocarcinoma. Unfortunately, there are many cases in which markers are available but the tumours are resistant to chemotherapy, so their use is not mandatory. Table 70.1 shows which markers have gained an established place in the repertoire of tests commonly offered by the clinical biochemistry laboratory.

Table 70.1

Clinical situations where tumour markers have been found to be useful

The future

Monoclonal antibodies raised against tumour cells and their membranes have led to the development of many new tumour marker assays, although few have as yet gained an established place in the management of patients with cancer. There is no doubt that tumour markers are an efficient and cheap way to monitor treatment. The search goes on for the ‘perfect’ marker that could be used in population screening, diagnosis, prognosis, monitoring treatment and for follow-up of tumour recurrence. However, the capacity for tumours to alter the expression of their surface antigens may make this goal unattainable.

Case history 56

A 72-year-old man, had complained of pains in his lower chest and abdomen for 2 months. His general practitioner detected dullness at both lung bases and referred him to a chest physician. On 23 June he was admitted to hospital. Examination revealed an enlarged liver. He had been a heavy drinker. Biochemistry results were:

• What is your differential diagnosis in the light of the liver function test results?

• How might AFP be of help in this case?

Comment on page 170.

Clinical note

Sometimes a man may be used as a negative control when his partner uses a pregnancy test kit at home. Teratoma of the testis has a peak incidence in men in their twenties, and this tumour frequently secretes large amounts of HCG. This will give rise to a positive pregnancy test in the man. Such a finding should be taken very seriously and followed up immediately.

Tumour markers

The main use of tumour markers is in monitoring treatment, although they may also be of use in screening, diagnosis, prognosis, and in long-term follow-up.

Calcitonin is used to screen the relatives and family of a patient with medullary carcinoma of thyroid.

AFP, paraproteins, prostate specific antigen and a variety of hormones are helpful in establishing the diagnosis of certain tumours.

AFP and HCG are of value in predicting the outcome of non-seminomatous germ cell tumours.

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