Tumour markers Flashcards
What makes a good tumour marker?
- A substance produced by, or in response to, a tumour
- Can be quantified
- Highly sensitive - so few people with the disease are missed AND
- Highly specific so that few people are falsely labelled as having the disease
Describe the 7 classes of tumour markers
- Cell-surface glycoproteins (CEA, CA125, CA19.9)
- Oncofetal proteins (human chorionic gonadotrophin, alpha-feta-protein)
- Enzymes
- Intermediate metabolites (vanillyl mandelic acid)
- Hormones (thyroglobulin, ADH, adrenocorticotrophic hormone)
- Immunogloublins (Light chains)
- Nucleic acids - DNA and RNA can be detected - Philadelphia chromosome, oncogene mutations, tyrosinase expression (a melanocyte-specific gene)
Describe the uses of tumour markers
- Diagnosis - after careful history and exam, they are expensive and can cause false positive (anxiety and over-investigation)
- CEA is elevated in many cancers but colorectal
- CA125 is also elevated in endometriosis, menstruation and pregnancy
- PSA is good because specific - Screening - NOT APPROPRIATE - their use has not altered outcomes found in RCT’s
- Prognosis - in testicular teratoma, concentrations of HCG or alphaFP are powerful determinants of outcome
- Response - most clinically useful feature - reduction in tumour marker is highly suggestive of a response
- Tumour relapse - can demonstrate, but don’t be overly reliant
Describe a situation where someone would be investigated with many tumour markers
CUP - especially young men presenting with multiple metastases
Have serum LDH, alpha-feta-protein and betaHCG to look for curable and chemo-sensitive cancers
Discuss CEA and it’s uses
CEA is a cell surface antigen, also expressed in a variety of normal tissues
Elevated in a number of tumours - clinical use in setting of colorectal cancer
The degree of CEA elevation is related to Duke stage - 4% in A, 65% in D
Describe other settings CEA will be raised
People who smoke, have IBD, hepatitis, pancreatitis or gastritis
Discuss CA125 and it’s uses
CA125 is a marker in OVARIAN carcinoma
It is an antigen expressed on the surface of ovarian cells
Discuss the sensitivity and specificity of CA125
Does not have perfect sensitivity and specificity - elevated serum found in 1% of women, 6% of women with benign conditions (pregnancy, PID), and 82% of women with ovarian cancer
CA125 is also elevated in pancreatic (59%), lung (32%), colorectal and breast cancer [usually when these have disseminated to the abdominal cavity]
Discuss alpha feto-protein (aFP) and it’s uses
aFP is a glycoprotein produced by the normal foetal yolk sac, liver and intestines
It is elevated in hepatocellular cancer, cancers containing yolk sac elements (teratoma), and hepatitis
Do high levels of aFP indicate a poor or good prognosis?
Poor
Discuss human chorionic gonadotrophin (HCG)
HCG is a glycoprotein consisting of two subunits
It is elevated in patient’s with gestational trophoblastic disease (hydatiform mole, choriocarcinoma)
There is also a specific elevation of the beta-subunit in patient’s with non-seminomatous testicular cancers and some seminoma (also raised in pregnancy)
Discuss PSA
PSA is a protein produced by prostatic cells
Levels are raised in prostate cancers, but also with benign hypertrophy of the prostate, trauma, rectal exam, prostatitis and UTI
Why can’t PSA be used for screening?
PSA lacks sufficient sensitivity and specificity to act as an accurate screening test - although it is often used to screen despite this evidence
What are the indicated uses of PSA?
- Monitoring response to hormonal and cytotoxic treatments
2. Surveillance after radical treatment
Discuss immunoglobulins and their uses
Immunoglobulins an be a measure of paraproteinaemias (e.g. Myeloma and Waldenstroms macroglobulinaemia), and occasionally non-Hodgkin’s lymphoma
They can be measured in the blood or their excretion can be measured as light chains in the urine (Bence-Jones protein), which occurs in 40-50% of myeloma
