Tumour Markers

1. Tumour Markers

2. Tumor Biology • Cancer cells behave as independent cells, growing without control to form tumors. Tumors grow in a series of steps. • The first step is:hyperplasia, meaning that there are too many cells resulting from uncontrolled cell division. These cells appear normal, but changes have occurred that result in some loss of control of growth. • The second step is :dysplasia, resulting from further growth, accompanied by abnormal changes to the cells. • The third step: requires additional changes, which result in cells that are even more abnormal and can now spread over a wider area of tissue.

3. Tumor Biology • These cells begin to lose their original function; such cells are called anaplastic. At this stage, because the tumor is still contained within its original location and is not invasive, it is not considered malignant — it is potentially malignant. The last step occurs when the cells in the tumor metastasize, which means that they can invade surrounding tissue, including the bloodstream, and spread to other locations. This is the most serious type of tumor, but not all tumors progress to this point. Non-invasive tumors are said to be benign.

4. The type of tumor that forms depends on the type of cell that was initially altered • . There are five types of tumors. • • 1-Carcinomas result from altered epithelial cells, which cover the surface of our skin and internal organs. Most cancers are carcinomas. • •2- Sarcomas result from changes in muscle, bone, fat, or connective tissue. • •3- Leukemia results from malignant white blood cells. • • 4-Lymphoma is a cancer of the lymphatic system cells that derive from bone marrow. • • 5-Myelomas are cancers of specialized white blood cells that make antibodies.

5. Tumour Markers • Cancer (tumour or malignant) cells produce abnormal substances. Usually these substances are not produced by normal cells. The abnormal substances produced by the cancer cells are enzymes, hormones and proteins. These substances are released into blood by cancer cells. • As a result their level in blood rises. Measurement of these substances in blood or serum provides useful information about cancer. Hence, they are called as tumour markers, Nowadays measurement of tumour markers in blood is an integral part of oncology.

6. Tumour marker measurement is used in • (a) Detection of cancer. • (b) Diagnosis of cancer. • (c) Prognosis of cancer. • (d) Determination of cancer stage. • (e) Determination of location of cancer in the body. • (f) Determination of organ involved in cancer. • (g) Cancer therapy.

7. Tumour markers

8. 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.

9. The use of tumour markers • Depending on the marker and the typeof malignancy, tumor markers may be used for screening, diagnosis, prognosis, therapy monitoring, and detecting recurrence. • Tumour markers can be used in different ways. They are of most value in monitoring treatment and assessing follow-up , but are also used in diagnosis, prognosis and screening for the presence of disease.

11. 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

12. 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.

13. 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.

14. 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.

15. Screening for the presenceof 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.

16. Types of Tumour markers • 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.

17. TYPES OF TUMOR MARKERS • Cancer can be detected and monitored using biologic • tumor markers. Tumor markers are produced either • directly by the tumor or as an effect of the tumor on • healthy tissue (host). Tumor markers encompass an array of diverse molecules such as : • 1-serum proteins, 2- oncofetal3-antigens, hormones, 4-metabolites, 5-Receptors, and Enzymes

18. 1-Enzyme tumor markers • A variety of enzymes are elevated nonspecifically in tumors . These elevated enzymes are largely a result of the high metabolic demand of these proliferative cells. Accordingly, enzyme levels tend to correlate with tumor burden, making them clinically useful for monitoring the success of therapy.

20. Serum protein tumor markers • Serum proteins, such as 2-microglobulin and immunoglobulins, are also used to monitor cancer therapy. 2-Microglobulin is found on the surface of all nucleated cells and can therefore be used as a nonspecific marker of the high cell turnover that is often observed in tumors. Immunoglobulins provide a more specific measure of plasma cell production of monoclonal proteins observed in hematologic malignancies such as multiple myeloma. Hormones and hormone metabolites are widely used as specific markers of secreting tumors

22. Hormones markers • Hormones and hormone metabolites are widely used as specific markers of secreting tumors . These hormones are particular valuable in diagnosing neuroblastomas, as well as pituitary and adrenal adenomas.

25. Oncofetal antigens tumor markers • One of the first tumor markers discovered was the oncofetal antigens. Oncofetal antigens such as carcinoembryonic antigen (CEA) and -fetoprotein (AFP) are expressed transiently during normal development and are then turned on again in the formation tumors

27. carbohydrate or cancer antigens tumor markers • Other tumor markers include monoclonal defined antigens, which were directly identified from human tumor extracts or cell lines. These are directed toward specific carbohydrate or cancer antigens and are best used for monitoring treatment of tumor that secrete these epitopes

29. Receptors tumor markers • Finally, receptors are used to classify tumors for therapy. These are the only “nonserologic” markers but are an important example of the diversity of tumor markers. Prototypic examples of such a marker are estrogen and progesterone receptors. When solid tumor biopsies are positive for these markers, tamoxifen chemotherapy is more likely to be effective.

31. Some clinically important tumour markers are • 1. α-Feto protein(AFP). It is a plasma protein and usually absent in normal people plasma. It is tumour marker for liver cancer and germ cell cancer. • 2. Calcitonin. It is a hormone. It is tumour marker for thyroid cancer. • 3. Carcino embryonic antigen (CEA). It is a protein and it is tumour marker for lung cancer, breast cancer, colon cancer and pancreas cancer. • 4.Human chorionic gonodotropin (HCG). It is tropic hormone. It is tumour marker • for germ cell cancer and trophoblast cancer.

32. Some clinically important tumour markers • 5.Acid phosphatase. It is tumour marker for prostate cancer. • 6.High mobility group chromosomal proteins (HMGCP). They are family of nonhistone chromosomal proteins that serve as architectural elements in chromatin . In normal tissues these proteins are expressed at very low levels. Their level is elevated in many human cancers. This small molecular weight proteins' expression is increased in neoplastic transformation of cells and metastatic of tumour progression.

33. Disadvantages of tumour markers • 1. These tumour markers usually detect cancer at advanced stage. So they are of little help in saving lives. • 2. A given marker is useful in the detection of only one type of cancer. • 3. Sometimes measurement of more than one type of tumour marker may be helpful or required.