Tumour Markers Flashcards
Definition of Tumour Marker
substances produced by tumour cells or by the host in response to a tumour
used to detect presence of tumour
can be found in cells, tissue or body fluids
measurable qualitatively or quantitatively
Sensitivity and Specificity
tests that are closer to the genetic basis of cancer are more sensitive and specific
DNA (BCR-ABL, HER2, EBV DNA) – Strange proteins (AFP, CEA, CA125, CA19-9) – Hormones (ADH, PTHrP, ACTH, hCG) – Tissue markers (PSA, Thyroglobulin) – General biochemical changes (LRFT, electrolytes, urate, LDH, ferritin etc)
Tumour specific = specific for single individual tumour
Tumour associated = found in different tumours of the same tissue type
Characteristics of an Ideal Tumour Marker
High sensitivity and specificity (organ specific)
Levels correlate with mass, severity, prognosis
Short half-life for rapid monitoring
Discriminatory to identify tumour from benign to healthy states
Adequate lead time for early diagnosis and Tx
==> screening, diagnosis, prognosis, monitoring, prediction of treatment response, detection of recurrence or relapse
Principles of screening and benefits/ risks
Principles:
- important health problem with accepted treatment, available facilities for Dx and Tx, recognisable latent or early symptomatic stage, suitable test that is acceptable to population, natural history of the condition is well known, established policy on who to treat, balance with costs
Benefits:
- improved prognosis
- less radical treatment needed for early disease
- reassurance if -ve
Risks
- longer morbidity
- over-treatment
- false reassurance if false negative
- anxiety and morbidity if false positive
Alpha-Fetoprotein (AFP)
Glycoprotein (heterogenous with varying degrees of glycosylation)
- one of the major proteins in foetal circulation
- synthesised by foetal liver and yolk sac
Produced by:
- HCC (esp AFP-L3 type)
- NSGCT (non-seminomatous germ cell tumours)
- Hepatoblastoma (in children)
- other types of advanced ADC
Uses:
- NSGCT - diagnosis, staging and monitoring (along with hCG and LDH); NOT FOR SCREENING
- HCC and Hepatoblastoma - aid Dx, monitoring and prognosis; SCREENING FOR HCC IN HIGH RISK, not in general population; NOT FOR METASTASIS
Interpretation of AFP
t1/2 = 5 days
Ref value: <10 microgram/L in healthy and non-pregnant
Screening in high risk for HCC
- surveillance with 6 monthly AFP and USG
- > 20 with rising trend = further Ix needed
- > 200 suggestive of HCC (virtually diagnostic if USG lesion >2cm present)
- > 400 = HCC if with any suspicious lesion
- > 1000 = symptomatic HCC patients
(most benign liver diseases <200)
Pregnancy
- maternal AFP increase from 12 wks, peak at 500 in 3rd trimester
- fetal AFP peak at 2 million at 14 wks and declines to 70000 at term
Infants
- extremely high (>10000)
- fall to adults levels between 6 mths and 1 yr – static levels may suggest underlying pathology
DDx of elevated AFP
Physiological
- infants
- pregnancy
Benign
- congenital disorders e.g. down’s
- childhood (citrin deficiency)
- liver cirrhosis, hepatitis, biliary tract obstruction, alcoholic liver disease, DILI
Malignant
- hepatoblastoma (children)
- NSGCT
- HCC
- other advanced ADC
Carcinoembryonic Antigen (CEA)
Cell-surface glycoprotein (also heterogenous in size)
- found in variety of normal and malignant epithelial tissues in GI, H&N, Lung and Breast
- also in foetal intestine, liver and pancreas
- may potentiate invasion and metastasis
Uses:
- post-treatment SURVEILLANCE of CRC –> serum CEA levels correlate with disease burden and is prognostic; NOT FOR SCREENING
- monitoring of other cancers as a tumour associated marker (metastatic cancers)
Interpretation of CEA
t1/2 = 3 days
Ref values: <3 mcg/L in non-smokers; <5 mcg/L in smokers
- non specific; benign conditions rarely cause CEA >10
- post-operative CEA elevation indicates recurrence with high probability
DDx of elevated CEA
Benign
- colon: IBD, polyps
- others: hepatitis, cirrhosis, alcoholic liver disease, obstructive jaundice, peptic ulcers, pancreatitis, bronchitis, renal, benign breast disease
Malignant
- colon: CRC
- others: CA lung, breast, stomach, pancreas, H&N
Human Chorionic Gonadotrophin (serum hCG)
Glycoprotein hormone (heterodimer with alpha and beta subunit – alpha similar to LH, FSH and TSH; beta unique)
Synthesised by syncytiotrophoblasts of placenta during pregnancy (maintain progesterone production of corpus luteum)
Produced by:
- germ cell tumours (e.g. testicular cancer) and trophoblastic diseases (hydatidiform mole, choriocarcinoma)
hCG secreted by tumours may be heavily glycosylated
Uses:
- diagnosis, follow up and prognosis in cancers
(also prenatal testing)
Interpretation of serum hCG
t1/2 = 36-48 hrs
Ref values: premenopausal, non-pregnant <1 IU/L; post-menopausal women <7; men <2
- serum hCG can be up to 25 in menopause
DDx of elevated hCG
Benign
- pregnancy
- pituitary hCG
- injection of hCG
- assay interferences
Malignant
- germ cell tumour (gonadal and extra-gonadal)
- gestational trophoblastic diseases (choriocarcinoma, hydatidifom mole)
- non-trophoblastic cancer (gyn, breast, GI, lung, GU, haematopoietic)
Prostate Specific Antigen (PSA)
Glycoprotein (serine protease)
- various molecular forms due to complex formation with protease inhibitors
- most PSA exists as COMPLEXED form; 10-30% free PSA
Produced EXCLUSIVELY by epithelial cells of acini and ducts of prostate gland
Uses:
- CA prostate – aid diagnosis, prognosis, surveillance, monitoring; SCREENING in men >50 yrs (value used is controversial)
Interpretation of PSA
t1/2 = 2.5 days after radical prostatectomyy
Ref values: total PSA <4 mcg/L; age specific values may give higher clinical sensitivity
<2.5 in 40-49
<3.5 in 50-59
<4.5 in 60-69
<6.5 in 70-79
Transient elevation in urological manipulation e.g. TURP, needle biopsy
– wait at least 6 weeks before testing!
