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TUMOUR MARKERS : AN

OVERVIEW
Indian Journal of Clinical
Biochemistry, 2007 / 22
(2) 17-31
T. Malati
Department of Biochemistry,
Nizam’s Institute of Medical
Sciences, Punjagutta,
Hyderabad- 500 082, India
TUMOUR MARKERS
• Synthesized in excess
concentration.
• Endogenous products or
products of newly
switched on genes.
• Excellent clinical relevance
in monitoring
• Early detection of cancer
CLASSIFICATION
1.Oncofetal antigens
e.g. AFP, CEA, Pancreatic oncofetal
antigen,
fetal sulfoglycoprotein.
2. Tumor associated antigens
/Cancer Antigens e.g. CA125,
CA19-9, CA15-3, CA72-4 CA50 etc.
7.Hormones
e.g.β-hCG
Calcitonin,
4. Hormone receptors
e.g. estrogen and
progesterone receptors
5. Enzymes and Isoenzymes
-PSA, PAP, NSE, PALP, TDT,
Lysozyme, alpha amylase
6. Serum and tissue proteins
-β-2microglobulin
-GFAP,
-protein S-100,
-ferritin,
-fibrinogen degradation products
7. Other biomolecules
e.g. polyamines
An ideal tumor marker
should have the following
criteria
1.Highly sensitive
2.Highly specific
3.Able to differentiate
between neoplastic and non-
neoplastic disease
4.Its levels should be
preceding the neoplastic
process
ALPHA FETOPROTEIN (AFP)
• It is expressed either during
malignancy or during intra
uterine or early postnatal life.
• <15 ng/ml.
• The clinical significance of AFP
- Prenatal diagnosis of open
spina bifida,
- Anencephaly,
- Atresia of esophagus and
THE ROLE OF AFP IN
MALIGNANCY
Diagnosis, prognosis and
monitoring of-
2.Primary hepatocellular
carcinoma
3.Hepatoblastoma,
4.Non-seminomatous testicular
germ cell tumors
8.Germ cell tumors of ovary and
extragonadal germ cell tumors
10.In malignancies of
HUMAN CHORIONIC
• AGONADOTROPIN (βHCG)
marker of germ cell tumors and
trophoblastic disease.
• Peak - 10th & 12th weeks of
gestation
• Men and non-pregnant women <5 IU
/ml and post-menopausal women
<10 IU /ml.
• HCG is a marker of first choice for
- gonadal choriocarcinoma and
extragonadal choriocarcinoma
CARCINO-EMBYRIONIC
ANTIGEN (CEA)
• Adenocarcinoma of the digestive
organs.
• Primary use in the detection of
local and metastatic cancer
recurrence.
• A persistently rising CEA value….
• A declining CEA value….
• Clinical relevance…
• Preoperative CEA level has
PROSTATE SPECIFIC
ANTIGEN (PSA)
• Gammaseminoprotein due to its
presence in seminal plasma.
• It is a monomer
• Prostate epithelium synthesizes
PSA
• PSA, a neutral serine protease
• The 100 KD PSA-ACT complex
• PSA-AT (alpha-1 antitrypsin)
• PSA-PCI (protease C inhibitor).
PROSTATE ACID
PHOSPHATASE (PAP)
• 200 times more abundant in
prostate tissue than in any other
tissue.
• Is useful only in staging
apparently localized disease i.e.,
primary prostate cancer before
definitive therapy such as
radical prostatectomy.
• The enzymatic assay appears
TUMOR ASSOCIATED
ANTIGENS
CA 125, CA 19.9, CA 15.3, CA
72.4 ETC

CANCER ANTIGEN 125 (CA


125)
•Detected by using murine
monoclonal antibody OC 125
•Epithelial ovarian carcinoma.
•In the serum, milk and
• Levels less than 35 U /ml in
serum
• Marker of first choice
adenocarcinoma ovary.
• Higher sensitivity for
nonmucinous epithelial ovarian
carcinoma.
• Breast (17.6%),
• 10.4% of benign
Colorectal ovarian tumors.
(15.1%),
Gastric (30.9%),
Esophagus (10.5%), Liver
(15.1%), Biliary
CA 19-9 (CANCER ANTIGEN 19-9)
• Pancreas and gall bladder
cancer.
• CA-19-9 are highest for the
adenocarcinoma pancreas.
• Acute and chronic Pancreatitis
CA 19-5 AND CA 50
• Colon, pancreatic and
hepatocellularcarcinoma
• Individually both antigens have
low sensitivity. However use of
both together improves
CA 15-3
CA 549
• Associated with breast
cancer
CYFRA 21-1
NSCLC such as SCC, adenocarcinoma and
large cell carcinomas.

• BETA -2 MICROGLOBULIN (β2M)


• B-cell leukemia, lymphomas and
multiple Myeloma. Monoclonal
CALCITONIN
-Increase in medullary carcinoma
of the thyroid, bronchogenic
carcinoma, small cell lung cancer,
breast, liver, lung, renal cancers
TISSUE POLYPEPTIDE ANTIGEN
(TPA)
• Moderate elevation in many diseases
and in pregnancy.
• The marked elevation in breast, lung,
gastrointestinal, urological, gynecological
cancer.
EPIDERMAL GROWTH FACTOR
RECEPTOR (EGFR)
• In SCC, breast cancer, gliomas, lung
cancer, blood cancer, and tumors of
female genital tract
ESTROGEN RECEPTOR (ER),
PROGESTERON RECEPTOR (PR)
• ER a 70 KD protein is present in
nuclei of mammary and uterine
tissues
• PR is a more sensitive indicator
than ER
HYDROXY INDOLE ACETIC ACID (5-
FERRITIN
•In advanced cancers of breast,
ovaries, lungs, colon and esophagus.
•In acute myelocytic leukemia,
teratoblastoma and SCC of head and
neck.
HOMOVANILLIC ACID (HVA) AND
VANILYLMANDELIC ACID (VMA)
-DETECTING AND MONITORING
THERAPY IN PATIENTS OF
PHEOCHROMOCYTOMA.
-THEIR MEASUREMENTS ARE ALSO
INTERLEUKIN-2 RECEPTOR / TAC
ANTIGEN (IL-2R)
• In some types of lymphoid
malignancies.
• In adult T-cell leukemia

TUMOR SUPPRESSOR GENE P53


• Commonly occurring P53 gene
mutations are reported in
primary breast, colon, ovarian,
lung, and esophageal
carcinomas.
• LIPID- • In breast, GIT, lung Ca,
ASSOCIA leukemia, lymphoma,
TED Hodgkin’s diseases and
melanoma.
SIALIC
• The slight increase of this
ACID IN marker is also observed in
PLASMA several inflammatory
(LASA-P) diseases.

• NEURON- • In glucagonomas,
SPECIFIC insulinomas, carcinoid
tumor,
ENOLASE pheochromocytoma,
(NSE) medullary carcinoma of
the thyroid, oat cell
ALTERATION OF SERUM BETA
2-MICROGLOBULIN IN ORAL
CARCINOMA
Indian Journal of Clinical
Biochemistry, 2002, 17 (2)
104-107
C.R.Wilma Delphine Silvia, D.M.
Vasudevan and K. Sudhakar
Prabhu.
Department of Biochemistry,
Kasturba Medical College, Manipal-
ABSTRACT
• Serum β2 –microglobulin (β2–m)
levels were measured in oral
carcinoma patients and
compared with normal healthy
controls.
• It was observed that there was a
significant rise in serum β2–
microglobulin in oral carcinoma
patients.
INTRODUCTION
• It was first described by
Berggard and Bearn in 1968
• β2 –microglobulin is a low
molecular weight, 11600 Dalton
protein found on the surface of
all cells except erythrocytes.
• It was also shown to occur in
small quantities in normal
human urine, plasma and CSF.
MATERIALS AND METHODS
• Patients and controls
• Exclusion criteria
• Group I: 20 healthy individuals, 8
females and 12 males.
• Group II: 4 oral keratosis, 3
males and 1
female.
• Group III: 30 oral carcinoma
patients, 17
• All patients were clinically
staged according to TNM staging
system of the International
union against cancer (UICC).
• This group of patients were
further divided into subgroups.
Group IIIA: 5 patients with stage
I oral cancer.
Group IIIB: 7 patients with stage
II oral cancer.
Group IIIC: 10 patients with
stage III oral cancer.
β2 –microglobulin
assay
• Serum.
• frozen at -70° C until assay.
• The serum was analyzed by
Enzyme linked
immunosorbent assay
• 2.4mg/L was used as the
upper limit, when 97% of
normal values are below this
Statistical analysis
• The data were analyzed by using
statistical package for social
sciences (SPSS) software.
• Cases and controls were tested
for statistical significance with
student’s ‘t’ test.
• Values of p<0.05 were
considered significant.
RESULTS
• The test showed an
abnormal result in only 1
out of 20 of healthy
controls and thus the
-specificity of 95.2%,
- positive predictive value
95%,
-negative predictive value
of 66.6%,
- and efficiency of the test
DISCUSSION
• Synthesized and secreted by
lymphocytes
• It has a low molecular weight
and rapid turnover
• Elevated levels of β2 –m have
been observed in a variety of
patients mostly with advanced
malignancy and other disease
states
• Serum β2 –m values were
increased in oral cancer
group, when compared with
controls, and this is
statistically significant
(p<0.05)
• The mechanism of increase in
β2 –m levels in malignancies
• It lacks specificity for oral
carcinoma as an individual
marker because it is elevated