BIOM346-Unit 3 (1) Cancer & Tumor Markers PDF

Unit 3: Cancer & Tumor Markers Dr. Elham Sharif, PhD Assistant Professor of Biomedical Sciences College of Health Sciences Qatar University  Chapter objectives  After attending two lectures on tumor markers, the students will:  Ident...

Unit 3: Cancer & Tumor Markers Dr. Elham Sharif, PhD Assistant Professor of Biomedical Sciences College of Health Sciences Qatar University  Chapter objectives  After attending two lectures on tumor markers, the students will:  Identify/Define tumor marker and explain the role of tumor markers in cancer management. (TL1)  Identify the characteristics or properties of an ideal tumor marker. (TL1)  Identify/State the major clinical value of tumor markers. (TL1)  Identify/Summarize the major tumors and their associated markers. (TL1)  Identify/Compare and contrast the major properties, methods of analysis, and clinical use of AFP, CA-125, CEA, beta-hCG, and PSA. (TL2)  Evaluate the use of enzymes and hormones as tumor markers. (TL2)  Interpret the biochemical data used in the investigation and diagnosis of disease, when given problem based case studies. (TL3)  Given a set of laboratory data and patient history, correctly diagnose the disease. (TL3) Dr Elham Sharif 10/23/17 2  Cell Dr Elham Sharif The cell is the basic unit of living organism. Groups of identical cells organised into a defined structure with specific function is known as tissues. Cells have different lineage and thus have different functions, but together they contribute to the overall structure of an organism. Two major cellular process involved in normal cell growth: o Differentiation: involves orderly progression of undifferentiated cells to produce a differentiated cells with specific function. o Proliferation: process where by cells increase in number by cell division Both process needs expression of various genes in controlled manner to maintain normal tissue structure and function. When a normal cells losses its ability to control the differentiation and proliferation pathways a transformed cell develops. 10/23/17 3  Cancer Is uncontrolled proliferation of cells that leads to tissue & organ dysfunction , system failure & death. Development of cancer is a multistep process that involves gradual loss of biological control over cell division. Cancer is staged based on: tumor size, histology, regional lymph node involvement, & presence of metastasis; 4 stages (I–IV). Dr Elham Sharif 10/23/17 4  Cancer staging and progression  Cancer (cont)  Multistep progression of normal cells to cancer, several steps occurs to genes involved in cell division.  The target for the genetic changes are:  Proto-oncogens: involved in promoting normal cellular division  Tumour suppressor genes: suppress normal cell division Proto-oncogenes products include proteins that normally function as: Growth hormones Growth hormone receptors Signal transduction molecules Cell cycle progression proteins DNA transcription factors. Dr Elham Sharif 10/23/17 6  Cancer (cont) Changes in the quantity or quality of proto-oncogenes can occur due to: o Point mutation & amplification o This result in defective or over-expressed onco-proteins o The mutated version of proto-genes found in the transformed cells are called oncogenes. Deletion or mutational inactivation of tumor suppressor genes also contribute to the transformed phenotype of cancer cells. The average number of genetic defects in proto-oncogens & tumor suppressor genes that converts the cell to a fully malignant phenotype is four to five. 10/23/17 7 Dr Elham Sharif  Classification of tumors A. Benign tumors o Suffix -oma o Name refers to tissue of origin Epithelioma, adenoma Examples: moles and uterine fibroids or fibromas, colon polyps Causes of Benign Tumors Environmental toxins, such as exposure to radiation Genetics Diet Stress Local trauma or injury Adrenal adenoma Inflammation or infection Dr Elham Sharif 10/23/17 8  Classification cont’d B. Malignant o Suffix -carcinoma epithelial cancers -sarcoma mesenchymal origin Adenocarcinoma of stomach Osteogenic sarcoma (bone) Adrenocortical carcinoma Dr Elham Sharif 10/23/17 9  Cancer-Neoplasm-tumor Benign Malignant Growth o Slow o Rapid o Unusual Haemorrhage o Often o Smooth Tumour edge o Irregular o No Secondary spread o Adjacent o Good Resemblance to o Poor original tissue o Uniform Cell size/ shape o pleomorphic o V. few Mitotic figures o many 10/23/17 Dr Elham Sharif 10  Damage to DNA  Chemical agents  Direct reacting  Metabolic activation  Physical agents  ionizing radiation  heat  Viral agents  DNA viruses  RNA viruses Dr Elham Sharif 10/23/17 11  Carcinogenesis Proto-oncogene Tumour suppressor gene controlled growth Dr Elham Sharif 10/23/17 12  Carcinogenesis Proto-oncogene Tumour suppressor gene Mutation oncogene Tumour suppressor gene Uncontrolled growth Dr Elham Sharif 10/23/17 13  Carcinogenesis Monoclonal in origin Failure to respond to regulation Autonomous growth Invasion Angiogenesis Metastatic growth Evasion Differentiation Dr Elham Sharif 10/23/17 14  Effects of cancer Physical o Compression, damage Biochemical o Protein, carbohydrate, lipid, calcium 90% of ppl with cancer have hypercalceimia Endocrine same o Eutopic cell o Ectopic outside cell Gene expression o Tumour markers Dr Elham Sharif 10/23/17 15  Tumour markers What are Tumor Markers？ How they are used Properties Classification Dr Elham Sharif 10/23/17 16  What are Tumor Markers？ TM is a cellular characteristic or substance produced by cancer cells, & can be used to differentiate tumor cells from normal cells. Origin: Produced by tumor directly or as an effect of tumor on tissue Most TM secreted into the circulation are not specific nor sensitive enough to be used for detection or screening of cancer, o because they are produced in various normal and benign tissues. you can’t use one tumor marker to make a diagnosis we need to have mutliple biomarkers to aid in the confirmation of a speicfic tumor TM are detected in: o a solid tumor, o circulating tumor cells in peripheral blood, o lymph nodes, in bone marrow, o other body fluid (urine, stool, ascites) 10/23/17 17 Dr Elham Sharif  How they are used? Potential Uses of Tumor Markers Population Screening Assessing differential diagnosis prostate cancer screening using psa for men over 50 Monitoring disease progression, Staging of cancer Estimating tumor volume Post-operative evaluation Monitor treatment response Surveillance for recurrence Evaluating response to drug treatment regimens Dr Elham Sharif 10/23/17 18  Timeline of tumor marker use  Update there is no ideal tumor marker however ideally we have certain markers signfying certain tumors Properties of an ideal TM Specificity for a single type of cancer High sensitivity for cancerous growths Correlate of marker level with tumour size Practical Short Half life of marker in circulation. Measured easily High analytical sensitivity of assay method High analytical specificity of assay method Cost-effective Test results contribute to patient care and outcome Dr Elham Sharif 10/23/17 20  Classification of Tumor Markers 1. Enzymes 2. Hormones & metabolites 3. Serum Proteins 1. :2-microglobulin & immunoglobulins 4. Oncofetal antigens: 1. carcinoembryonic, alpha-fetoprotein 5. Carcinoma associated antigens 6. Genetic defects 7. Receptors: o non-serologic; estrogen & progesterone receptors Dr Elham Sharif 10/23/17 21  Tumour markers 1. Enzymes Tissue damage Tumour related, tissue specific enzymes example is porstate specific antigen Tumour specific enzymes Dr Elham Sharif 10/23/17 22  Paget's disease of bone is a condition involving cellular remodeling and deformity of one or more bones. gland increases in a conidtion called bengin prostatic H Dr Elham Sharif 10/23/17 23 https://slideplayer.com/slide/10579781/  Neuroendocrine Tumors Neuron-specific enolase (NSE) o A neuronal isoenzyme of the cytoplasmic enzyme enolase, found in neuroendocrine cells o Used as a prognostic factor in neuroblastoma o Occur in neuroendocrine tumors: medullary carcinoma of the thyroid, pheochromocytoma, carcinoid tumors; immature teratoma, 65~85% with small cell carcinoma of lung, ~38% with non-small-cell lung cancer, and melanoma. o Correlate with stage and bulk of disease 10/23/17 24 Dr Elham Sharif  update Prostate Specific Antigen (PSA)/Tissue specific antigen Introduction/Description Is a serine protease of 33-kd glycoprotein produced only in epithelial cells of acini & in prostatic ducts Function: o Produced by epithelial cells of the prostate gland and secreted into seminal plasma o It is a Glycoprotein protease that functions in liquefaction of seminal coagulum, Dissolves cervical mucous cap, allowing sperm to enter. Regulates seminal fluid viscosity Regulation/Physiology Low levels of PSA can be detected in serum of healthy men. Forms of PSA found in blood: o 1) Enveloped by protease inhibitor, a2-macroglobulin; this lacks immunoreactivity. o 2) Complexed to another protease inhibitor, antichymotrypsin PSA-ACT; immunologically detectable. o 3) Free PSA, not complexed to protease inhibitor; immunologically detectable o 4) Total PSA assays measure complexed and free PSA forms, as they are immunologically detectable. Dr Elham Sharif 10/23/17 25  Prostate Specific Antigen (PSA) (cont’d) o Clinical Application/Interpretation Annual screening of prostate cancer in men over 50 years old & in younger men at high risk (family history) PSA is a sensitive & accurate indicator of Pca. PSA is very useful for monitoring pts following prostatectomy. The sensitivity and specificity of PSA as a marker are limited because; o PSA is detectable in the plasma of normal men, o its concentration increases both with increasing age and in benign prostatic hypertrophy (BPH) (common problem of elderly men). o Digital rectal examination may  plasma PSA conc. slightly and transiently, o but significant  can occur in both acute urinary retention and prostatitis. Dr Elham Sharif 10/23/17 26  Digital rectal examination DRE palpable nodules consistency surface (regular or irregular) Dr Elham Sharif 10/23/17 27  Prostate Specific Antigen (PSA) (cont’d) Prostate cancer detection: Age Serum PSA 1) Early detection guidelines endorse lower cutoff of PSA (ng/ml) up to 2.5 ng/mL. 40~50 0~2.5 2) PSA > 2.5 ng/mL perform biopsy 3) PSA velocity is measurement of the rate of change per 50~60 0~3.5 year. 60~70 0~4.5 a) Biopsy recommended when PSA rises more than ‫اذا زاد بهاملعدل‬ 0.75 ng/mL/year even when PSA is