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Tumour Markers Annual Practice Nurse Conference 2016 Kate Murphy (OLN) & Aoife O’Shea (Research Nurse) Tumour Markers The concept of tumour markers can mean anything that helps in the diagnosis of cancer In a more restricted sense it refers to the biochemical detection of cancer. Definition of a tumour marker • Tumour markers are substances produced by cancer or by other cells in the body in response to cancer or certain benign conditions • These substances can be found in the blood, urine, stool, tumour tissue or other bodily fluids of some patients with cancer • Used to help detect, diagnose and manage some types of cancer – usually combined with other tests (biopsies, scans etc.) Tumour Marker Uses • Tumour markers are not diagnostic in themselves • A definitive diagnosis of cancer is made by looking at tissue biopsy specimens under a microscope • However, tumour markers provide information that can be used to screen (PSA in prostate ca), diagnose (Ca125 in ovarian cancer), stage, determine prognosis and guide treatment Limitations of Tumour Markers • No “universal” tumour marker that can detect all types of cancer, has been found • Non-cancerous conditions can cause the levels of certain tumour markers to increase • Not everyone with cancer will have a high level of a tumour marker associated with that cancer • No tumour marker identified to date is sufficiently sensitive or specific to be used on its own to screen for cancer Limitations of tumour markers • Screening asymptomatic patients • Screening patients with a strong family history of cancer • Screening patients with known cancer causing mutation e.g. ovarian cancer (Ca125 (BRCA)) H.S.E Guidelines • If tumour markers were taken recently, do not repeat • Be specific – send tumour markers relevant to the malignancy that is expected • If likely unknown cancer origin, testing multiple markers is rarely useful • Do not take at night or over weekends • A normal level does not exclude malignancy and an abnormal may occur in a patient with no malignancy Tumour Marker Groups • Tumour markers can be classified in two groups: 1. Cancer specific markers 2. Tissue specific markers Cancer Specific Markers • Related to the presence of certain cancerous tissue – These markers might not be specific in making a diagnosis – Useful in the follow-up of treated patients – To describe progress of the disease – Response to treatment Examples of these markers are CEA, Ca 15.3, Ca 125 & Ca 19.9 Examples of Cancer Specific Markers • • • • • • • • Metastatic Breast Cancer – CA 15.3 Colon Cancer – CEA Prostate Cancer – PSA Ovarian Cancer – CA 125 Pancreatic Cancer – CA 19.9 Non-Hodgkin's Lymphoma – LDH Testicular Cancer – AFP, Beta HCG, LDH Multiple Myeloma – Beta 2 Microglobulin, Serum Protein Electrophoresis (SPEP), Immunoglobulins and Kappa and Lambda light chains How are cancer specific markers used? • They are measured periodically during cancer therapy • A decrease in level may indicate response to treatment • No change or an increase may indicate that the cancer is not responding • May also be used after treatment has ended to check for recurrence (return of cancer) Carcinoembryonic Antigen (CEA) • A blood-borne protein, first noted to be produced by tumours of the gastrointestinal system • It can also be produced in lung and breast cancer • Rarely elevated in early disease CEA cont…. • Elevated levels do not necessarily mean a bowel cancer (cirrhosis, inflammatory bowel disease, hepatitis) • Rising CEA levels can be an early sign of recurring bowel cancer • Normal Range - <5.0ng/mL CA15.3 • Breast cancer (metastatic only), lung, ovarian and pancreatic • Also elevated in benign breast conditions and sometimes inflammatory bowel condition • Stage disease, monitor treatment and determine recurrence • Normal Range = <31.3 IU/mL CA 125 • Used for Ovarian cancer • Elevated in endometriosis and some other benign diseases • Help diagnose, monitor treatment and determine recurrence • Normal Range = <35 IU/mL CA 19.9 • Elevated in gastric, colon and pancreatic cancer • Also in hepatocellular and bile-duct cancer • Non cancerous conditions that may increase CA19-9 include gallstones, pancreatitis, cirrhosis of liver and cholecystitis • Normal Range = 0 - 37 IU/mL LDH • lactate dehydrogenase (LDH) • when tissues are damaged by injury or disease, they release more LDH into the bloodstream. • Normal Values = 125-220 IU/L Elevated LDH • CVA • Drugs: anaesthetics, aspirin, narcotics, procainamides, alcohol • Haemolytic anaemia • Pernicious anaemia’s • Infectious mononucleosis (glandular fever) • Intestinal and pulmonary infarction (tissue death) • • • • • Kidney disease Liver disease Muscular dystrophy Pancreatitis Lymphoma and other cancers Tissue Specific Markers • Related to specific tissues which have developed cancer - these substances are not specifically related to the tumour, and may be present at elevated levels when no cancer is present. - But unlike the previous group, elevated levels point to a specific tissue being at fault PSA • Often used as a screening test for prostate cancer in men but can be elevated in prostatic hypertrophy, prostatitis, urinary retention & post TURP • Debate among experts and national organizations over the usefulness of this test for screening asymptomatic men • Not clear if PSA screening outweighs the harm of followup diagnostic tests • Normal Range - <4.0 ng/mL Human Chorionic Gonadotropin (HCG) • Elevated in testicular and trophoblastic disease • Elevated in pregnancy, testicular failure • Help diagnose, monitor treatment, and determine recurrence Alpha-Feto Protein (AFP) • Elevated in liver, germ cell cancer of ovaries or testes • Elevated during pregnancy • Help diagnose, monitor treatment and determine recurrence AFP cont.. • AFP is measured in pregnant women through the analysis of maternal blood or amniotic fluid, as a screening test for a subset of developmental abnormalities • Increased in open neural tube defects and omphalocele • Decreased in Down syndrome. Beta-2 Microglobulin • Multiple myeloma and lymphomas • Elevated in Cohn's disease and hepatitis • Determine prognosis Calcitonin • Thyroid medullary carcinoma • Can be elevated in Pernicious anaemia and thyroiditis • Help diagnose, monitor treatment, and determine recurrence Gene mutations • Some people are at a higher risk for particular cancers because they have inherited a genetic mutation • While not considered tumour makers, there are tests that look for these mutations in order to estimate the risk of developing a particular type of cancer • BRCA1 and BRCA2 are examples of gene mutations • Related to an inherited risk of breast cancer and ovarian cancer Monoclonal Immunoglobulins • Elevated in Multiple myeloma and Waldenstrom’s macroglobulinaemia • Overproduction of an immunoglobulin or antibody, usually detected by protein electrophoresis • Help diagnose, monitor treatment, and determine recurrence (blood and urine) Conclusion • No tumour marker identified to date is sufficiently sensitive or specific to be used on its own to screen for cancer • A normal level does not exclude malignancy and an abnormal may occur in a patient with no malignancy Questions