Transcript In body fluids

Historical background of tumor markers
• The first TM reported was Bence Jones protein. Since its
discovery in 1847 by precipitation of a protein in acidified
boiled urine , the measurement of B.J.P has been a
diagnostic test for Multiple myloma (plasma cell tumor).
• The general application of TM for monitoring cancer
patient start with the discovery of AFP in 1963 and CEA
in 1965.
Definition of TM
• A substance produced or induced by tumor cells
and released into blood , body fluids or
expressed on cell surface , that can be used to
differentiate a tumor from normal tissue or to
determine the presence of a tumor.
• Few markers are specific for a single individual
tumor
( tumor-specific markers )
• Most are found with different tumors of the same
tissue type
(tumor-associated markers )
Classification of TM
•
•
•
•
•
•
•
Enzymes & isoenzymes
Hormones
Oncofetal antigens
Carbohydrates markers
Proteins
Receptors & other markers
Genetic markers
(Oncogenes & suppressor gene mutations )
Potential uses of TM
•
•
•
•
•
•
•
Screening in general population
Clinical staging of cancer
Prognostic indicator for disease progress
Evaluation of treatment success
Detection the recurrence of cancer
Monitoring response to therapy
Radioimmunolocalization of tumor
Recommended Cancer Screening
Tests
Cancer
Technique
Breast
Mammography
CRCA
Sigmoidoscopy
Cervical
PAP
Neuroblastoma
VMA
HCC
AFP
Prostate
PSA
Ovarian
CA 125
Predictive Markers
ER and PR: For predicting response to
hormone therapy in breast cancer
HER-2: For predicting response to
trastuzumab (Herceptin) in breast cancer
Disease Management
• Most TM are used to monitor treatment and
progression of cancer .
• Single determination does not allow definite
conclusion.
• Combining different markers can improve the
diagnostic precision.
• Normal level ( negative result ) does not exclude
malignancy.
Enzymes & Isoenzymes
TM
cancer
Aldolase
Liver
Amylase
Pancreatic
Alp
Liver, Bone, leukemia & lymphoma
CK-BB
Prostate, lung , breast, colon, ovary
LDH
Liver, leukemia & lymphoma
GGT
Liver
PSA&PAP
Prostate
Elastase
breast
Hormones
TM
cancer
ACTH
Cushing’s & Lung
ADH
Lung, adrenal cortex, pancreas
PTH
Liver, renal, breast, lung
Calcitonin
Medullary thyroid
Gastrin
Glucagonoma
GH
Pituitary, renal , lung
hCG
choriocarcinoma
Prolactin
Pituitary, renal , lung
Oncofetal Ags :Normally produced proteins during
fetal life, decrease to low levels or disappear after
birth and reappear in cancer patients
TM
cancer
AFP
HCC, germ cell carcinoma
CEA
Colorectal, GIT, pancreas, lung, breast
Carcinofetal
ferritin
Liver
Squamous cell
Ag
Cervix, lung, skin, head & neck
Carbohydrate markers:
Either are antigens on the tumor cell surface or are
secreted by the tumor cells
They are high molecular weight mucins or blood group
antigens
TM
cancer
CA 125
Ovarian , endometrial
CA 15-3
Breast , ovarian
CA 19-9
Pancreatic , gastrointestinal , hepatic
CA 19-5
Gastrointestinal , Pancreatic , ovarian
CA 50
Pancreatic , gastrointestinal , colon
Proteins TM
TM
cancer
B2-microglobulin
MM ,B-cell lymphoma ,CLL
C-peptide
Insulinoma
Ferritin
Liver, lung, breast, leukemia
immunoglobulin
MM , lymphomas
Other tumor markers
TM
Nature
Cancer
Estrogen &
progesterone
receptors
Tissue
Breast
Catecholamine
metabolites
Urine ( VMA , HVA )
Nuroblastoma ,
phyochromocytoma
Hydroxypoline
Urine
Bone metastasis
(breast) , MM
Genetic Markers
•
1.
Two classes of genes are involved in the development
of cancer :
Oncogens :
cell activation genes that code for products involved in
normal cellular processes such as growth factor
signaling pathways.
over expression ( activation ) of oncogens will lead to
abnormal cell growth , resulting in malignancy (mostly
hematological malignancy ).
Some oncogens found in human tumors
oncogen
function
cancer
N-ras mutation
Signal
transduction
AML,
nuroblastoma
K-ras mutation
Signal
transduction
Leukemia,
lymphoma
bcl-2
Blocks apoptosis
Leukemia,
lymphoma
2. Suppressor genes
Genes involved in the recognition and repair of damaged
DNA.
The loss of function of this genes cause inability of DNA
repair and lead to tumor formation ( mostly solid tumors )
.
The oncogenicity is derived from the loss of the gene rather
than activation .
Some S. genes found in human tumors
gene
cancer
P53
MUTATION
Breast , colorectal , lung , liver , renal
BRCA1
MUTATION
Breast , melanoma
BRCA2
MUTATION
Breast
RET
Medullary thyroid cancer
Genetic Testing for Cancer
Susceptibility
Genetic testing should be carried out:
# If the individual has personal or family history
suggestive of cancer susceptibility
# If the test can be adequately interpreted
# If the test will aid the diagnosis or influence the
or medical or surgical management of the patient
family members
J Clin Oncol 2003;21:1
How to identify tumor marker ?
On cell
Cytochemistry, Flow cytometry
On tissue
Histochemistry, Cytosol assays
In body fluids
Blood, urine, CSF, Amniotic fluid