Biochemistry – Tumor Markers

TUMOR MARKERS

Tumor markers are specific biomolecules created by the body as a metabolic or immune response of a healthy cell to the presence of a malignant cell, or they are produced by malignant cells as component biomolecules of the malignancy. Tumor markers may be enzymes, specific proteins, various antigens, hormones, specific receptors, etc. Today, there have been discovered over 100 different tumor markers, however, only about twenty of them are used in laboratory practice.

ELEVATED TUMOR MARKERS

Most frequently, elevated tumor markers indicate to tumor cell proliferation (both malignant and benign) in the body, however, they may also occur with certain inflammatory diseases. If the cause of elevated tumor markers is an inflammatory disease, when the inflammation ceases, tumor marker levels fall to normal. Conversely, if elevated tumor markers are a result of tumor cell proliferation, the levels will not fall, but constantly increase, until the tumor disease has been detected and adequately treated.

HOW AND WHEN TO DEFINE TUMOR MARKERS?

Tumor markers are usually determined in blood, urine or tissue samples using various laboratory methods.

Tumor markers should be determined when a person is healthy. Each person has his/her on standard (basic or initial) value for each tumor marker separately.

Determining tumor marker levels may be performed during the diagnosis; before, during or after completion of a therapy; and periodically, to determine possible tumor recurrence.

If a tumor marker is determined in order to examine the effectiveness of a therapy or to see if there was worsening of the underlying disease or tumor recurrence, its levels should be determined periodically in certain intervals (to see if its levels increase or reduce). These STANDARD determinations are certainly far more important than the individual measuring of tumor marker levels.

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CAN TUMOR MARKERS BE USED AS SCREENING TESTS FOR DETERMINING MALIGNANT TUMORS (CANCER)?

Screening tests are the tests which enable us to make a diagnosis before symptoms occur. Detecting a tumor at an early stage is very important because it indicates that the tumor has not spread yet and that there is no metastasis, and that the treatment is easier and more successful. In order for a test to be valid in terms of screening, it must have high specificity and sensitivity. Most tumor markers do not have sufficient specificity or necessary sensitivity to use them for the screening of malignant diseases.

CAN TUMOR MARKERS BE USED FOR DIAGNOSING MALIGNANT TUMORS?

Tumor markers can not be used to diagnose cancer. The best standard for diagnosing a malignant disease is BIOPSY (taking a sample of tumor tissue, followed by various histopathological techniques which are used for proving the presence of tumor cells that can be seen under a microscope). In case a malignant process has well advanced at the moment of discovering the tumor, determination of tumor markers can be used to detect a primary tumor (i.e. where the process started). For example, if a woman has a malignant tumor which permeates the entire abdomen and pelvis, and has an increased CA 125, it is likely that the tumor is of ovarian origin (even in the case when a surgeon is unable to distinguish what the original place of the cancer is). This is crucial for deciding on the protocol and type of therapy.

Alfa-feto protein (AFP) is an example of a tumor marker which can help in the diagnosis of liver cancer. The level of this tumor marker may be increased in various liver diseases, but if it reaches a certain high level, the doctor may be pretty sure that this is a malignant process.

CAN TUMOR MARKERS BE USED FOR DETERMINING AGRESSIVE TREATMENT AND FOR MAKING FORECASTS FOR SPECIFIC TYPES OF A TUMOR?

Some types of malignant tumors grow and spread faster than other. Even within a tumor of the same tissue origin, specific types are more aggressive, or have a tendency to grow and show metastasis (spreading to the surrounding and distant tissues), but also less sensitive to specific therapeutic procedures and protocols. Sometimes the level of a tumor marker can predict the behaviour and “look” of specific types of tumors. For example, with testicular cancers, high levels of tumor markers HCG and/or AFP predict more aggressive cancer and a lower cure or survival rate. Treatment of the patients with such high levels of tumor markers should start more aggressively and with higher doses of chemotherapy drugs and radiation.

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HOW TUMOR MARKERS CAN BE USED FOR DETERMINING SUCCESS OF A TREATMENT?

One of the major roles of determining the concentration of tumor markers is monitoring success of applied treatment procedures (particularly with advanced malignancy). If a tumor marker is determined before and after a treatment, and at the same time there was a significant decrease in its concentration, this means that the applied treatment protocol was very successful. All other procedures for treatment assessment such as X-ray, magnetic resonance imaging, scanner, etc. are much more expensive and have a greater risk for human health. On the other hand, if the applied treatment increases tumor marker levels, this is a sign of inadequate treatment and it must be modified. The only exception is the case of enormous sensitivity to specific chemotherapy drugs, when the drug destroys in a short time a large number of malignant cells and causes release of huge amounts of markers in the blood, leading to a SHORT-TERM increase in its levels.

CAN TUMOR MARKERS BE USED FOR DETERMINING RECURRENT TUMORS?

Yes, they can. Tumor markers can be used to detect recurrent tumors after completion of a therapy even when there are still no signs or symptoms of it. This may be done even before the tumor is proved with imaging techniques. This usually refers to the following tumor markers:

  • Prostate specific antigen (PSA) for prostate cancer,
  • Human chorionic gonadotropin (HCG) for gestational trophoblast tumors and certain gestation cell tumors,
  • Alfa-feto protein (AFP) for liver cancer and germ cell tumors,
  • CA 125 for ovarian tumors,
  • Carcinoma embryonic antigen (CEA) for colon cancer.

In such cases, periodic, serial determination of tumor markers has greater significance than individual and random performance of the same analyses. In addition, it is recommended to COMPARE RESULTS OF TESTS CONDUCTED IN THE SAME LAB, and also always ensure that levels are expressed in the same units (ng/mL, U/mL, and similar units).

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