Lecture 4

Special chemistry Definition Special Chemistry is a subsection of the Chemistry Laboratory of the Division of Clinical Pathology. This includes the tests which are not the part of the routine panel.  Electrophoresis  Urine chemistry  Radioimmunoassay.

Test Sensitivity and specificity Troponin test The most sensitive and specific test for myocardial damage. Because it has increased specificity compared with CK-MB, troponin is a superior marker for myocardial injury. Myoglobin (Mb) low specificity for myocardial infarction. Rises very early within 1-3 hours of pain. Pro-brain natriuretic peptide (pro-BNP) This is increased in patients with heart failure. It has been approved as a marker for acute congestive heart failure Glycogen phosphorylase isoenzyme BB high sensitivity and specificity early after chest pain. by ELISA Normal troponin levels 12 hours after chest pain has started mean a heart attack is unlikely

Myloperoxidase (MPO)  Elevated in chronic conditions CRP  Marker of atherosclerosis Pregnancy associated plasma protein A (PAPPA)  elevated in atherosclerosis when atheroma is about to rupture Oxidized LDL  A marker of atherosclerosis Choline  Test of prognosis  Rises in chest discomfort even without rise in troponin level.

Tumour markers A substance produced by tumour or by the host in response to tumour from normal tissues. May be present in blood, urine or tissues. Mostly they are antigens May be cytoplasmic proteins, enzymes and hormones.

uses  Screening  Example: elevated prostate specific antigen suggests prostate cancer.  Monitoring of cancer survivors after treatment. Example: elevated AFP  Diagnosis of specific tumor types, particularly in certain brain tumors and other instances where biopsy is not feasible

Be specific to the tumor Level should change in response to tumor size An abnormal level should be obtained in the presence of micrometastases The level should not have large fluctuations that are independent of changes in tumor size Levels in healthy individuals are at much lower concentrations than those found in cancer patients Predict recurrences before they are clinically detectable Test should be cost effective Ideal tumour marker

SCREENING TESTS Cancer must be common The natural history of the cancer should be understood Effective treatments must be available The test must be acceptable to both patients and physicians The test must be safe and relatively inexpensive

GUIDELINES FOR ORDERING/ INTERPRETING TUMOR MARKER TESTS Never rely on the result of a single test Order every test from the same laboratory Consider half-life of the tumor marker when interpreting the result. Consider how the Tumor Marker is removed or metabolized Consider Hook Effect Consider presence of HAMA antibodies

Detection techniques

Detection technique Tumor markers can be detected by immunohistochemistry Tissue selection Fixation. Tisue slicing by microtome. Antigen antibody reaction. Antibodies are labeled with some substance for detection enzyme, flurophore etc. Amplification

COMMON TUMOR MARKERS AnalyteCancer Use CEAMonitor colorectal, breast, lung cancer CA-125Ovarian cancer monitoring AFPGerm cell tumors, liver cancer Total PSA Screen and monitor prostate cancer Free PSADistinguish prostate cancer from BPH HCGGerm cell and trophoblastic tumors Hormone receptor Breast cancer therapy

Benign conditions leading to high tumour marker level MarkerAssociated nonmalignant conditions AFPViral hepatitis, liver injury, IBD, pregnancy β-hCGTesticular failure, pregnancy CEA Smokers, IBD, hepatitis, cirrhosis, pancreatitis,gastritis CA 125 Peritoneal irritation, endometriosis, pelvic inflammatory disease, hepatitis, pregnancy PAP / PSAProstatitis, benign prostatic hyperplasia

CEA Described by Gold and Freedman in 1965 as a marker for Colorectal Cancer Glycoprotein with a carbohydrate composition ranging from % of molecular mass CEA levels times upper limit of normal suggests colon cancer CEA is not used to screen for colon cancer

AFP Tumour marker of hepatocellular carcinoma, as well as in the acute and chronic hepatitis. Level is less than 10 ng/ml. In person with no liver disease level upto 400ng/ml means liver cancer. But in patients with infections levels upto 4000ng/ml means liver cancer. If tumour is removed fully with surgery then its level should go back to normal. After surgery if level rises again then it means that tumour is back.

Tumor-associatedProteinsImmunoglobulins, markersβ-2M EnzymesLactate dehydrogenase, alkaline phosphatase, pteridines, pterines Acute-phaseC-reactive protein, proteinsferritin InflammatoryESR, viscosity makers UltrastructuralIntermediateDesmin, vimentin componentsfilament components