Tumors & tumor markers. Dr. Attila Miseta University of Pécs, Faculty of Medicine, Departmet of Laboratory Medicine 2016
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1 Tumors & tumor markers Dr. Attila Miseta University of Pécs, Faculty of Medicine, Departmet of Laboratory Medicine 2016
2 Tumors Tumor: abnormal mass of tissue and tissue growth The tumor has no useful function, rather it interferes with normal tissue function. Hematological diseases!?
3 Tumors The tumor disease The problem of a single cell (tissue), which is later the problem of the whole body.
4 Diagnosis The tumor associated symptomes are different depending on the site and size and the type of the tumor. Shorter or longer asymptomatic or noncharacteristic periods are frequent. The primary goal is early diagnostics! 1. Clinical examination, 2. Imaging techniques (CT, MRI, PET), 3. Biopsy, (lab markers).
5 Tumormarker Definition Molecules originating from the tumors, which enter the body fluids and may be quantitatively analyzed by non invasive methods. (5th Conference on Human Tumor Markers, Stockholm, Sweden, 1988)
6
7 Generation of tumor markers Tumor cell Extracellular space Intravasal space
8 Laboratory diagnostics in tumor diseases Tumor markers Aspecific, side symptoms Paraneolasia: metabolic, electrolyte, hematology, hemostasis, ectopic hormones, etc. Molecular biology Based dignostics: prevention, prognostic, therapy
9 Tumor markers I. Main characteristics: 1. The tumor markers are molecules (frequently proteins), which are generated in the tumor cells. Alternatively, the presence of tumor induces other (non-tumor) cells to generate tumor specific molecules (i.e. tumor markers). 2. There is a reference range for every tumor marker. This is the case because tumor markers are synthesized in normal cells too. When compared to other laboratory parameters, the significance of absolute numbers is negligible. The tumor marker levels before surgery, irradiation, or chemotherapy (pretherapeutic levels) must be noted and compared to posttherapeutic levels.
10 3. Oncofetal antigens, carbohydrate epitopes of glycoproteines, ectopic hormones, abnormal immunglobulines, enzymes (isoenzymes), etc. 4. Tumor marker detection may be characterized with low sensitivity and specificity. They are (usually) not suitable for screening. 5. Tumors are diagnosed by physical examination or by imaging primarily. The main applications of tumor markers involve prognosis, therapy monitoring and early detection of recurrence.
11 6. It is important to label the measurement method. (Different reference ranges.) 7. Samples must be forwarded to the laboratory ASAP. Disintegration of blood cells might elevate the levels of some tumor markers (NSE). Chemotherapy or irradiation may increase tumor marker levels trough increased decomposition of cells.
12 Tumor marker CEA AFP CA 19-9 Indication colorectal carcinoma breast cancer hepatocellular cancer testicular cancer hepatobiliar cancer pancreas cancer Characteristics 180kDa glycoprotein, ca. 50% carbohydrate 70kDa glycoprotein, ca. 4% carbohydrate Lewis antigen epitope MCA breast cancer 350Da mucin like protein CA 125 ovarian cancer 200 kda glycoprotein, ca. 25% carbohydrate CA 72-4 gastric cancer, ovarian cancer 400 kda mucin like glycoprotein CA 15-3 breast cancer 300 kda mucin like protein PSA prostate cancer 33 kda glycoprotein, serin protease hcg NSE CYFRA germ cell tumors, trophoblast tumors small cell lung cancer, endocrin tumors non small cell lung cancer glycoproteohormone, α/ß chains, 14/24 kda 87 kda, enolase isoenzyme 30 kda cytokeratin 19 fragment SCC squamous cell cancer 42 kda glycoprotein, tumor antigen
13 Medical Genetics Studies the transfer of traits between generations of organisms. The methods based on genetic principles are widely used to diagnose genetic and non-genetic diseases. Diagnosis Therapy Tremendous practical importance The future
14 Diagnostic uses I. To show the presence of an invading organism: Viruses. Slow or not growing, or intracellular bacteria. Other bacteria that are prone to be lost during sample delivery. II. Manifest genetic deseases of the early childhood. Genetic deseases that are becoming manifest during adulthood DNS hibák (mutációk). Genetic factors which predispose to various genetic deseases. III. Identification: archeological, family, criminal IV. Toxicology.
15 Hereditary Mutations Egg Sperm Mutation Occurs Fertilized Egg Mutation Reproductive Bone Pancreas Body Cells of Offspring Brain
16 Acquired Mutations Normal Bone Cell Mutation Occurs Altered Gene Altered Bone Cells Normal Bone Cells
17 Many Mutations Lead to Cancer Normal Cell First Mutation Second Mutation Third Mutation Fourth or Later Mutation Malignant Cells
18 Types of genetic tests Cytogenetic DNS (RNS) Metabolic
19 Related exam questions 1. The most important laboratory tests that suggest the presence of malignant diseases (erythrocyte sedimentation rate, metabolites, enzyme activities, etc.) 2. Tumor markers and their informational value (AFP, CEA, enzymes, hormons, etc.) 3. Measurement of multidrug resistance in the clinical laboratory
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