Clinical case: A 47 year old man presented to a physician with history of yellowing of the eyes. The doctor requested for “serum tumour markers”The following were done by the laboratory:
WHAT IS LIKELY DIAGNOSIS?
| TEST | RESULT | REF. RANGE |
| CA-15.3 | 215 | 0 -25U/ml |
| CA 19.9 | 2855 | < 37U/ml |
| AFP | 98 | <8.5 ng/ml |
| CEA | 361 | 3-5 ng/ml |
| CA 125 | 176 | <35U/ml |
Introduction
- Cancer is a public health problem worldwide.
- 12% of all deaths in the world are due to cancer.
- It is the second most common cause of death in developed countries.
- Increased life expectancy contributing.
- HIV-AIDS causing increased risk of certain cancers in developing countries.
- Most cancers are not curable.
- Overall cancer mortality has not changed significantly over the last 40 years.
- Prevention and Early detection of cancer offers best chance of effectively reducing cancer deaths in the future.
- Early diagnosis is difficult because: Patient may not have symptoms ad Diagnostic procedures may not be sensitive enough.
- (Many radiological procedures detect tumours at least 1-2cm in size >1billion cells).
Tumour markers are:-
- Substances found in cells or body fluids produced by tumour, or the host in response to presence of tumour they are Used to differentiate tumour from normal tissue or determine the presence of tumour.
Types of tumour markers:-
Cellular tumour markers – Antigens located on cell membranes e.g hormone receptors, or genetic changes
Humoral tumour markers – Substances which can be detected in body fluids (serum, urine, pleural etc). They are secreted by tumour tissue, or by the host as a reaction to presence of the tumour
Classification of tumour markers
- Enzymes
- Hormones
- Oncofetal proteins
- Carbohydrate epitopes
- Proteins
- Receptors
- Oncogene products
Enzymes
Alkaline phosphatase – Bone, liver, Leukemia
Prostatic acid phophatase – Prostate
Prostate specific antigen – Prostate
Hormones
- ACTH – Lung
- Calcitonin – Medullary carcinoma Thyroid
- hCG – Testicular (nonseminoma), Choriocarcinoma, Embryonal.
- Prolactin – Pituitary
Oncofetal antigens
α- fetoprotein – Liver, germ cell tumours
CEA – Colorectal, breast, pancreas
Squamous cell carcinoma antigen (SCC) – Cervix, lung, skin
Tissue polypeptide antigen (TPA) – breast, ovary, bladder.
Carbohydrate epitopes
- CA 125- Ovary
- CA15.3 – Breast, ovary
- CA19.9 – Pancreas, GIT
Proteins
- Immunoglobulins – Multiple myeloma, lymphoma
- β2-Microglobulin – Myeloma, lymphoma
- C- peptide – Insulinoma
- Ferritin – Liver, lung, breast.
Other markers
Oestrogen/progesterone receptors – Breast
Catecholamine metabolites-Phaeochromocytoma Oncogenes
c-myc translocation – lymphoma
c-erb B2 amplification (HER-2) – Breast
bcl-2 – Leukemia, lymphoma
Criteria for usefulness of tumour markers:-
- High sensitivity – detectable when only few cancer cells present.
Sensitivity = True positive results
true +ve + false –ve results.
- High specificity – not detectable in healthy individuals or in non-malignant disease.
Specificity = True negative results
True –ve + false -ve results.
Clinical Applications of tumour markers
- Screening for cancer
Current usefulness: Limited
Reasons:
- Marker should be elevated at early disease stage
- Marker should be specific for the tumour.
Most markers are not suitable for this.
May be effective if incidence of cancer is high in population screened.
Can be used in high risk populations e.g α-FP in chronic liver disease, PSA in men over 40 yrs.
- Diagnosis of cancer
Limited usefulness
Requires high specificity.
Most markers not tissue specific.
exceptions PSA.
- Staging of cancer
Limited usefulness
Some markers are related to disease stage
PSA > 50ug/L usually indicates tumour has extended beyond the prostate.
- Determining Prognosis
Limited usefulness
Low Accuracy. Not all tumours elaborate markers.
- Treatment monitoring
Important use
Evaluating success of therapy
Detection of recurrence
Requires serial determination of tumour marker
interpretation of serial tumour marker values