1. Dr. Amal S. Ahmed Ass Prof.Clinical Pathology Suez Canal University
Tumor Markers
Dr. Amal S. Ahmed
Ass Prof.Clinical Pathology
Suez Canal University

2. 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.

3. 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 )

4. Classification of TM Enzymes & isoenzymes Hormones Oncofetal antigens
Carbohydrates markers
Proteins
Receptors & other markers
Genetic markers
(Oncogenes & suppressor gene mutations )

5. 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

6. Recommended Cancer Screening Tests
Technique
Cancer
Mammography
Breast
Sigmoidoscopy
CRCA
PAP
Cervical
VMA
Neuroblastoma
AFP
HCC
PSA
Prostate
CA 125
Ovarian

7. 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

9. 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.

10. Enzymes & Isoenzymes cancer Liver Aldolase Pancreatic AmylaseTM
Liver
Aldolase
Pancreatic
Amylase
Liver, Bone, leukemia & lymphoma
Alp
Prostate, lung , breast, colon, ovary
CK-BB
Liver, leukemia & lymphoma
LDH
GGT
Prostate
PSA&PAP
breast
Elastase

11. Hormones Cushing’s & Lung ACTH Lung, adrenal cortex, pancreas ADH
cancer TM
Cushing’s & Lung
ACTH
Lung, adrenal cortex, pancreas
ADH
Liver, renal, breast, lung
PTH
Medullary thyroid
Calcitonin
Glucagonoma
Gastrin
Pituitary, renal , lung GH
choriocarcinoma
hCG
Prolactin

12. Oncofetal Ags :Normally produced proteins during fetal life, decrease to low levels or disappear after birth and reappear in cancer patients
cancer TM
HCC, germ cell carcinoma
AFP
Colorectal, GIT, pancreas, lung, breast
CEA
Liver
Carcinofetal ferritin
Cervix, lung, skin, head & neck
Squamous cell Ag

13. Pancreatic , gastrointestinal , hepatic CA 19-9
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

14. Proteins TM cancer MM ,B-cell lymphoma ,CLL B2-microglobulin
Insulinoma
C-peptide
Liver, lung, breast, leukemia
Ferritin
MM , lymphomas
immunoglobulin

15. Other tumor markers Cancer Nature TM Breast Tissue
Estrogen & progesterone receptors
Nuroblastoma , phyochromocytoma
Urine ( VMA , HVA )
Catecholamine metabolites
Bone metastasis (breast) , MM
Urine
Hydroxypoline

16. Genetic Markers
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 ).

17. Some oncogens found in human tumors
cancer
function
oncogen
AML, nuroblastoma
Signal transduction
N-ras mutation
Leukemia, lymphoma
K-ras mutation
Blocks apoptosis
bcl-2

18. 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 .

19. 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

20. 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

21. How to identify tumor marker ?
On cell
Cytochemistry, Flow cytometry
On tissue
Histochemistry, Cytosol assays
In body fluids
Blood, urine, CSF, Amniotic fluid

23. Thank you