Tumor Markers

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
Technique

Cancer

Mammography

Breast

Sigmoidoscopy

CRCA

PAP

Cervical

VMA

Neuroblastoma

AFP

HCC

PSA

Prostate

CA 125

Ovarian

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
Liver

Aldolase

Pancreatic

Amylase

Liver, Bone, leukemia & lymphoma

Alp

Prostate, lung , breast, colon, ovary

CK-BB

Liver, leukemia & lymphoma

LDH

Liver

GGT

Prostate

PSA&PAP

breast

Elastase

Hormones
TM

cancer

Cushings & Lung

ACTH

Lung, adrenal cortex, pancreas

ADH

Liver, renal, breast, lung

PTH

Medullary thyroid

Calcitonin

Glucagonoma

Gastrin

Pituitary, renal , lung

GH

choriocarcinoma

hCG

Pituitary, renal , lung

Prolactin

Oncofetal Ags :Normally produced proteins

during fetal life, decrease to low levels or
disappear after birth and reappear in cancer
patients
TM

cancer
HCC, germ cell carcinoma

AFP

Colorectal, GIT, pancreas, lung, breast

CEA

Liver

Carcinofetal
ferritin

Cervix, lung, skin, head & neck

Squamous cell Ag

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
cancer

TM

Ovarian , endometrial

CA 125

Breast , ovarian

CA 15-3

Pancreatic , gastrointestinal , hepatic

CA 19-9

Gastrointestinal , Pancreatic , ovarian

CA 19-5

Pancreatic , gastrointestinal , colon

CA 50

Proteins TM
TM

cancer
MM ,B-cell lymphoma ,CLL

B2-microglobulin

Insulinoma

C-peptide

Liver, lung, breast, leukemia

Ferritin

MM , lymphomas

immunoglobulin

Other tumor markers

Cancer

Nature

TM

Breast

Tissue

Estrogen &
progesterone receptors

Nuroblastoma ,
phyochromocytoma

Urine ( VMA , HVA )

Catecholamine
metabolites

Bone metastasis
(breast) , MM

Urine

Hydroxypoline

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

cancer

function

oncogen

AML, nuroblastoma Signal transduction

N-ras mutation

Leukemia,
lymphoma

Signal transduction

K-ras mutation

Leukemia,
lymphoma

Blocks apoptosis

bcl-2

Suppressor genes. 2
.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

cancer

gene

Breast , colorectal , lung , liver , renal

P53
MUTATION

Breast , melanoma

BRCA1
MUTATION

Breast

BRCA2
MUTATION

Medullary thyroid cancer

RET

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 medical or surgical management of the patient
or 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

Thank you