Tumour markers Flashcards
What are tumour markers?
Used in cancer diagnosis
Usually measured in body fluids or tissues
More than 20 available
Usually a protein
Where do tumour markers come from?
Either produced
- directly by cancer cells
- by the body in response to the presence of cancer cells
What are examples of tumour markers?
CEA
HER2/ neu
AFP
PSA
What is HER2/ neu?
Expressed in certain cancers of the breast, stomach and oesophagus
Detected via biopsy using immunohistochemical staining
Used to determine prognosis and guide treatment
HER2/neu-positive cancers tend to grow/spread faster than other cancers
More likely to respond to treatment with drugs that work against the HER2 receptor on cancer cells
What is AFP?
Major serum protein in the developing embryo
Expression quickly declines in the months after birth
Can become elevated in certain cancers of the liver, ovaries and testes
Measured using a blood test
Monitoring helps diagnose, monitor treatment and detect recurrence
What is PSA?
Measured via blood test
Used to screen, helps diagnose, monitor treatment and detect recurrence of prostate cancer
Used to screen men at high risk due to family history
Not specific to prostate cancer: may also be elevated in benign prostatic hyperplasia, prostatis and increasing age
What is CEA?
Carcinoembryonic antigen
Normally produced in the gastrointestinal tissue in the developing embryo - believed roles in cell adhesion
Group of related gycoproteins
Found in fetal colon
Found in very low levels in normal population, raised in patients with colorectal cancer
Who first discovered CEA?
Gold and Freedman
In 1965
Antigen present in foetal colon and colon adenocarcinoma
Appeared to be absent from healthy adult colon
Which cells produce CEA in normal population?
Colon my mature columnar cells
Released into the gut lumen and disappears with the faeces
Not high levels are found in the blood
Which cells produce CEA in colon cancer cases?
Malignant cells have no basal lamina and have lost their polarity
CEA is distributed around the cell surface membrane
Continually exfoliated away in plasma membrane-derived vesicles which end up in the blood via draining lymph and blood vessels
Can CEA be used to diagnose all cases of colon cancer?
Less likely to produce CEA in poorly differentiated tumour
Cells no longer look like colon cells
CEA not useful as tumour maker
What does the histology of normal colon look like?
Mucosa contains deep crypts bordered by a single-layer of columnar epithelium
Epithelial cells are constantly sloughed off into the lumen and are replaced by new cells
What does the histology of colon adenocarcinoma look like?
Muscularis mucosa is infiltrated by abnormal neoplastic glandular tissue
What are the limits of CEA?
Not useful in mass screening programme
The aim of the mass screening programme is to detect colorectal cancers early
Large proportion of early stage colorectal cancer would not be detected by CEA concentration in the blood
Lead to unacceptably high numbers of false negative results
Due to low sensitivity
What is the sensitivity and specificity of CEA?
Using an upper limit of normal of 2.5 microg/L
CEA has
- sensitivity: 36%
- specificity: 87%
Which factors could give false positive results in CEA?
Smokers
Irritable bowel syndrome
Others cancers
- lung
- breast
- liver
- pancreas
- thyroid
- stomach
- ovaries
Peptic ulcers
Ulcerative colitis
Rectal polyps
Benign breast disease
Emphysema
What is sensitivity?
Measure of the proportion of positive results gained by people who do have the condition
How good is the test at identifying those with the condition?
What is specificity?
Measure the proportion of negative results gained by people who do not have the condition in question
How good is the test at identifying those without the condition?
What is a false negative?
People testing negative who do in fact have the condition
What is false positive?
People testing positive who do not have the condition
What are the two uses of measuring CEA in colorectal cancer?
CEA measured to see if the cancer has come back
CEA measured to see if the cancer is responding to chemotherapy
How can CEA be used to see if the cancer has come back?
CEA is measured before resection of the colorectal cancer
The aim of CEA monitoring after curative resection of colorectal cancer is to detect recurrent disease at an early and treatable stage
- before the patient notices it has come back
- give treatment for the early stages of the disease = more successful
How can CEA be used to see if the cancer is responding to chemotherapy?
Patients who exhibited a decrease in CEA while on chemotherapy had better overall survival
Increases in CEA while on chemotherapy predicts progressive disease - cancer is still growing
Clue before the scans show any change to the cancer shape/size
What sample is used to measure CEA levels?
Plasma or serum
Occasionally another body fluid like peritoneal, pleural or cerebrospinal is collected for testing
Presence of CEA in other body fluids may indicate metastasis to that system
What department analyses CEA levels?
Clinical biochemistry
What assay is used to measure CEA levels?
Chemiluminescent Magnetic Immunoassay
What machine measures CEA levels?
Automated modular analyser
What assay is used to measure CEA levels?
Chemiluminescent magnetic immunoassay
What are the three components of CMIA?
Utilises
- the specificity of immune-complex formation
- the detectability of chemiluminescence
- the ease of separation possible with magnetism
What is used in CMIA?
An immune complex sandwich is made from two types of antibody
Using CEA protein from the sample (50 microl) as the filling
The two antibodies that bind to the sample to form the sandwhich:
- ruthenium-labeled antibody
- biotin-labeled antibody
Streptavidin-coated magnetic microparticles are added
These bind to sandwich complex via biotin
How do we measure CEA levels with CMIA?
The mixture is tranderred to the measuring cell
Complexes are magnetically captured onto the surface of an electrode via streptavidin
Application of voltage through the electrode generates an unstable excited electron state in the ruthenium complex
Upon relaxation to the lower-level state photons are released
The amount of light generated is proportional to the amount of CEA in the sample
Measured by a photomultiplier
The CEA concentration is calculated using a calibration curve
What happens to the sandwich complex when voltage is applied?
Application of voltage stimulates and electrochemiluminescent reaction between ruthenium and a substance in the buffer called TPA
Results in the emission of light
What is the turnaround of CEA concentration measurement?
1 day
What is the reference range of CEA levels?
< 2.5 microg/L
< 5.0 microg/L in smokers
