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General information on tumour markers

In these pages we try to explain the text of the guidelines on the use of tumor markers, ment for professionals, in a way that patients who want to know a bit more about these tests can understand their possibilities in a better way.

The term "tumor markers" refers to substances that can be produced and /or released by tumor cells to the blood stream and special laboratory methods are available to measure them in blood samples taken from one of the blood vessels in for example your arm.


Measuring tumor markers in general is not considered a reliable diagnostic test for screening on the presence of a tumor that was not known to exist. However, elevated levels of tumor markers can be of help in specific situations to help in making a choice for additional diagnostic laboratory tests, X-rays or  technically even more advanced scans.
In patients with confirmed cancer, knowledge about the level of a tumor marker can be of help to monitor the effect of treatment by comparing the levels in your blood  before and after treatment.
Some tumor markers are more strongly associated to specific cancers than others.
  The usefullness of a tumor marker will depend primarily on the specificity and  sensitivity of the test, which may be explained as follows:

Specificity: The percentage of normal persons or persons with benign conditions for whom a negative result is obtained.
The greater the specificity, the fewer the false-positives.
Or in other words:
If the specifity of a test is very high this means that an elevated level of the marker is a good reason to consult your doctor for additional tests in search for the disease.

Sensitivity: The percentage of test results which are correctly positive in the presence of a tumour.
The greater the sensitivity, the fewer the false-negatives.
Or in other words:
If the sensitivity of a test is very high this means that most patients with the disease will show a positive test result.

 

In situations where tumor spots from unknown origin are found, for instance in the bones or liver or brain, the use of tumor marker tests can be of help to narrow down the possible type of cancer and be of help in making a choice for therapy. (Table 1).

It is important to remember that no tumor marker is specific for a single type of cancer and that also other disorders may result in elevated levels of a tumor marker.
If the liver or kidneys are not functioning well, this may be a reason that the tumor marker is not properly removed from the blood and that small quantities accumulate, giving rise to a false positive test result.
And in addition it is important to remember that, if the specificity and/or sensitivity of the marker is low or intermediate, a "normal" tumor marker result does not exclude the presence of cancer.

Of course you are aware that every person is slightly different from the other. This is true also for the exact levels of tumor markers. A single measurement and test result can not provide the same information as multiple determinations at different time points.
Important are the changes that can be observed.
If an elevated tumour marker level in test 1 has normalised in test 2 some weeks later, this might indicate that the first one was false positive. Ask your doctor if also other lab tests such as liver function or renal function tests have changed.
On the other hand if a second test result after some weeks is higher ( more than double) than the first. It is appropriate to ask for additional tests to rule out the presence of a tumor.
In situations where a tumor marker was elevated before the treatment started, a drop towards normal levels or even below that, is a good indication of successfull treatment.
In the event that the initial treatment has been a success, you may discuss with your doctor to measure during the follow up control visits the same tumor marker that was elevated before treatment. A serial test result with rising values may indicate a recurrence of the cancer at an early stage, sometimes even before other symptoms are evident. Take the liberty to discuss with your doctor what to do when such a recurrence knocks on your door.
There might be a good argument to do additional investigations to confirm the recurrence. Another option is to discuss with your doctor if you could benefit from a change of therapy if available.
In situations where both patient and doctor know and accept that there is no alternative approach for therapy, it might be wise to decide together not to continue measuring the tumor marker.
However, this may differ again from person to person in the way the patient uses the knowledge of an elevated tumor marker. Such knowledge may also prevent a request for additional, expensive and sometimes very inconvenient investigations.

Many tumor marker tests were formerly performed in specialist laboratories, but with the development of automated immunoassays, they are now often available in routine laboratories. Results are consequently more readily available to non-specialist clinicians, who may be less familiar with their interpretation. If this would be the case in your situation and you have the impression that your questions are not answered with clear explanations, this website offers you the possibility to consult one of our experts, free of charge.

This, coupled with increasing pressure on laboratories to reduce costs, and on clinicians to practice "evidence-based medicine", encourages critical appraisal of how to achieve best use of these tests. This is being undertaken by numerous groups, including the European Group on Tumour Markers. Conclusions reached by its Focus Groups are summarised in the following papers. General recommendations about quality requirements for tumor marker measurements will be summarised first, before discussing recommendations about how tumor markers should best be used for different malignancies. The order of the papers is as indicated below:

  • Quality requirements and control
  • Germ cell cancer
  • Prostate cancer
  • Breast cancer
  • Gynaecological cancer
  • Gastrointestinal cancer
  • Lung cancer

Table 1. Characteristics of tumour markers discussed in these articles

  Biochemical properties

Molecular weight

Primary clinical applications
Alpha-fetoprotein (AFP) Glycoprotein, 4% carbohydrate; considerable homology with albumin

~70 kD

Diagnosis and monitoring of primary hepatocellular carcinoma and germ cell tumours. Prognosis of germ cell tumours.
Cancer antigen 125 (CA125) Mucin identified by monoclonal antibodies

~200 kD

Monitoring ovarian carcinoma. Prognosis after chemotherapy.
Cancer antigen 15.3 (CA15.3, BR 27.29) Mucin identified by monoclonal antibodies

>250 kD

Monitoring breast cancer
Cancer antigen 72.4 (CA72.4) Glycoprotein identified by monoclonal antibodies

~48 kD

Monitoring gastric carcinoma
Cancer antigen 19.9 (CA19.9) Glycolipid carrying the Lewisa blood group determinant

~1,000 kD

Monitoring pancreatic carcinoma
Carcinoembryonic antigen (CEA) Family of glycoproteins, 45-60% carbohydrate

~180 kD

Monitoring gastrointestinal and other adenocarcinomas
CYFRA 21-1 Fragments of cytokeratin 19

~30 kD

Monitoring bladder and lung carcinoma.
Estrogen receptor Nuclear transcription factor

65 kD

Predicting response to endocrine therapy in breast cancer.
Human chorionic gonadotrophin (hCG) Glycoprotein hormone consisting of two non-covalently bound subunits (a and b)

~36 kD

Diagnosis and monitoring non-seminomatous germ cell tumours, choriocarcinomas, hydatidiform moles, seminomas. Prognosis of germ cell tumours.
Neuron specific enolase (NSE) Dimer of the enzyme enolase

~87 kD

Monitoring small cell lung carcinoma, neuroblastoma, apudoma
Placental alkaline phosphatase (PLAP) Heat-stable isoenzyme of alkaline phosphatase

~86 kD

Monitoring of germ cell tumours (seminomas)
Progesterone receptor Nuclear transcription factor

A form: 94 kD

B form: 120 kD

Predicting response to endocrine therapy in breast cancer.
Prostate specific antigen (PSA) Glycoprotein serine protease

~36 kD

Diagnosis, screening and monitoring prostatic carcinoma
Squamous cell carcinoma antigen (SCC) Glycoprotein sub-fraction of tumour antigen T4

48 kD

Monitoring squamous cell carcinomas
Tissue polypeptide antigen (TPA) Fragments of cytokeratin 8, 18 and 19

~22 kD

Monitoring bladder and lung carcinoma
Tissue polypeptide specific antigen (TPS) Fragment of cytokeratins 18

~22 kD

Monitoring metastatic breast carcinoma

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