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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
• 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