Tumour Markers

1. Tumour Markers Annual Practice Nurse Conference 2016 Kate Murphy (OLN) & Aoife O’Shea (Research Nurse)

2. 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.

3. 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.)

4. 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

5. 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

6. 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))

7. 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

8. Tumour Marker Groups • Tumour markers can be classified in two groups: • Cancer specific markers • Tissue specific markers

9. 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

12. 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

13. 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)

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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 Elevated LDH

21. 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

22. 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 follow-up diagnostic tests • Normal Range - <4.0 ng/mL

23. Human Chorionic Gonadotropin (HCG) • Elevated in testicular and trophoblastic disease • Elevated in pregnancy, testicular failure • Help diagnose, monitor treatment, and determine recurrence

24. Alpha-Feto Protein (AFP) • Elevated in liver, germ cell cancer of ovaries or testes • Elevated during pregnancy • Help diagnose, monitor treatment and determine recurrence

25. 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.

26. Beta-2 Microglobulin • Multiple myeloma and lymphomas • Elevated in Cohn's disease and hepatitis • Determine prognosis

27. Calcitonin • Thyroid medullary carcinoma • Can be elevated in Pernicious anaemia and thyroiditis • Help diagnose, monitor treatment, and determine recurrence

28. 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

29. 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)

30. 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

31. Questions