This document discusses special chemistry tests and tumor markers. It defines special chemistry as tests not part of routine panels, including electrophoresis, urine chemistry, and radioimmunoassay. It describes the sensitivity and specificity of troponin, myoglobin, and pro-brain natriuretic peptide for detecting heart damage and failure. It also discusses various tumor markers like CEA, AFP, PSA, and their uses for screening, monitoring cancer survivors, and diagnosing certain tumors. Guidelines are provided for ordering and interpreting tumor marker tests. Common detection techniques include serology, enzyme assays, immunoassays, and genetic analysis.

1. Lecture 4

2. 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.

3. 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

5. 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.

6. 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.

7. 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

8. 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

9. 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

10. 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

11. Detection techniques
Serology Enzyme assays
Immunological Immuno histo chemistry
Radio immuno assay
Enzyme-linked immuno sorbent assay
Flow cytometry
Cytogenetic analysis Fluorescent in-situ hybridization
Spectral karyotyping
Comparative genomic hybridization
Genetic analysis Sequencing (automated)
Reverse transcription
Gel electrophoresis
DNA micro-array analysis
Proteomics
Surface-enhanced laser
desorption/Ionization

12. 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

13. COMMON TUMOR MARKERS
Analyte Cancer Use
CEA Monitor colorectal, breast, lung cancer
CA-125 Ovarian cancer monitoring
AFP Germ cell tumors, liver cancer
Total PSA Screen and monitor prostate cancer
Free PSA Distinguish prostate cancer from BPH
HCG Germ cell and trophoblastic tumors
Hormone
receptor
Breast cancer therapy

14. Benign conditions leading to high tumour
marker level
Marker Associated nonmalignant conditions
AFP Viral hepatitis, liver injury, IBD, pregnancy
β-hCG Testicular failure, pregnancy
CEA
Smokers, IBD, hepatitis, cirrhosis,
pancreatitis,gastritis
CA 125
Peritoneal irritation, endometriosis, pelvic
inflammatory disease, hepatitis, pregnancy
PAP / PSA Prostatitis, benign prostatic hyperplasia

15. CEA
Described by Gold and Freedman in 1965 as a
marker for Colorectal Cancer
Glycoprotein with a carbohydrate composition
ranging from 50 - 85% of molecular mass
CEA levels 5 - 10 times upper limit of normal
suggests colon cancer
CEA is not used to screen for colon cancer

16. 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.

18. Tumor-associated Proteins Immunoglobulins,
markers β-2M
Enzymes Lactate
dehydrogenase,
alkaline phosphatase,
pteridines, pterines
Acute-phase C-reactive protein,
proteins ferritin
Inflammatory ESR, viscosity
makers
Ultrastructural Intermediate Desmin, vimentin
components filament components