Tumor markers are substances produced by tumor cells or the body's response to tumors that can be detected and measured in blood, urine, or body tissues. They can be used to screen for cancers, help diagnose cancer, determine prognosis, stage cancer, detect recurrence, and monitor treatment effectiveness. Common tumor markers include enzymes, hormones, oncofetal antigens, carbohydrates, blood group antigens, proteins, and receptors. Examples are PSA for prostate cancer, CEA for colorectal cancer, CA125 for ovarian cancer, and AFP for liver and germ cell cancers. Tumor marker levels can indicate the presence, location, and spread of cancer as well as how well cancer treatment is working.

1. Tumor markers

2. What is tumor marker?
• Any substance which can be related to
the presence or progress of a tumor
• A tumor marker is substance
– Produced by tumor or
– Produced in relatively large quantities by malignant
cells than non-malignant cells or
– Produced by host in response to a tumor
• Used to determine the presence of a
tumor based on measurements in the
blood or secretion

3. Applications of tumor marker
1. Screening of cancer
2. Diagnosis of cancer
3. Evaluating cancer prognosis
4. Tumor staging
5. Detection of tumor recurrences
6. Monitoring effectiveness of cancer therapy
(more imp. usefulness).

4. Techniques used in assessment of Tumor Marker
1. Chemical or enzymatic method
2. Enzyme immunoassay (EIA)
3. Radio immunoassay (RIA)
4. Immunofluorescent assay (IFA)
5. Chemiluminencent immuno assay (CLIA)
6. Flow cytometry

5. Classification of tumor markers
1. Enzymes
2. Hormones
3. Oncofetal antigens
4. Carbohydrate markers
5. Blood group antigens
6. Proteins
7. Receptors
8. Gene

6. 1. Enzyme as tumor marker
• Alcohol dehydrogenase (Liver)
• Aldolase (Liver)
• Alkaline phosphatase (bone, liver, leukemia, sarcoma)
• Alp-placental (ovarian, lung, trophoblastic,
gastrointestinal, seminoma etc.)
• Amylase (pancreatic, various)
• Gamma-GT (liver)
• LDH (liver, lymphoma, leukemia)
• 5’-Nucleotidase (liver)
• PSA (prostate Specific Antigen)
• Prostatic specific phosphatase
• Neuron specific Enolase

7. 2. Hormones as tumor marker
1. ACTH
2. ADH
3. Calcitonin
4. Gastrin
5. GH
6. hCG
7. Human placental lactogen
8. Neurophysins
9. PTH
10. Prolactin
11. Vasoactive intestinal peptide

8. 3. Oncofetal antigen as tumor marker
1. AFP
2. β-oncofetal antigen
3. CEA
4. Tissue polypeptide antigen

9. 4. Carbohydrate marker
1. CA 125
2. CA15-3
3. CA 549
4. CA 27.29

10. 5. Blood group antigen
1. CA 19-9
2. CA 19-5
3. CA 50
4. CA 72-4
5. CA 242

11. 6. Protein as tumor marker
1. β2-microgolbulin
2. C-peptide
3. Ferritin
4. Immunoglobulin
5. Thyroglobulin
6. Bence Jones Protein

12. 7. Receptors as tumor markers
1. Estrogen and progesterone receptors
2. Androgen receptor
3. Hepatocyte growth factor receptor(c-MET)
4. Epidermal growth factor receptor

13. 8. Genes as tumor marker
•Oncogene
(cell activation genes)
•Suppressor gene
(gene involved in the recognition and repair of
damaged DNA)

14. BRIEF DISCUSSIONS ON SOME TUMOR MARKERS

15. I. Enzymes as tumour markers
A. Alkaline phosphatase [ALP]
• ALP is mainly present in liver, biliary tract, bone and
placenta
• Increased ALP can be seen in
– liver cancer
– Cancer of biliary tract
– Metastatic cancer with bone or liver involvement
– testicular seminomas

16. B. Lactate dehydrogenase [LDH]
• Elevated LDH can be seen in variety of cancer
including liver, non-Hodgkin’s lymphoma,
leukemia, neuroblastoma etc
• LDH correlates with tumor mass in solid
tumors and provide a prognostic indicator for
disease progression

17. C. Prostate Specific Antigen [PSA]
• Prostate cancer is the third most common cancer in
men world-wide
• The measurement of serum PSA is a cornerstone of
the standard of care for detection of prostate cancer
(PCa)
• PSA is a serine protease exclusively produce by
epithelial cells of the acini and duct of prostate
• PSA is one of the most promising tumor marker for
diagnosis and screening of Pca and monitoring
treatment as well.
• Unfortunately PSA is tissue specific but not tumor
specific therefore also elevated in BPH

18. PSA contd.
• Single chain glycoprotein.
• Free PSA or complexed with α1
antichymotrypsin and α2 macroglobulin.
• Most immunoassays measure both free and
PSA- α1 antichymotrypsin complex but not
PSA- α2 macroglobulin.
• Sandwitch immunoassay mostly used to
measure PSA.

19. II. Hormones as Tumor Marker
• Tumor of endocrine cells result excess production of
hormones.
Insulin – Insulinoma
GH – Tumor of somatotropes
PRL- prolactinoma
Catecholamines and its derivatives- pheochromocytomas
etc.

20. A. Human chorionic gonadotrophin (hCG)
• hCG is a hormone produced by the normal placenta,
reaching a maximum concentration in plasma by the
eighth week of pregnancy
• The presence of hCG in the plasma (non-pregnant)
indicates the presence of abnormal trophoblastic tissue
or a tumor secreting the hormone ectopically
• Ideal tumor marker for choriocarcinoma, a malignant
proliferation of chorionic villi that may develop from
hydatidiform mole.

21. hCG CONT’D
• Glycoprotein secreted by syncytiotrophoblast cells of
normal placenta.
• Two dissimilar α and β subunits.
• The α subunit similar to several other hormones: LH,
FSH and TSH.
• Useful in monitoring treatment and progression of
trophoblasic disease.
• Patients with trophoblastic tumors: >1 million IU/L.
• Sandwitch immunometric format mostly used for
assay.

22. III. Oncofetal antigens as Tumor marker
A. α-Fetoprotein (AFP)
• synthesized by the yolk sac and the fetal liver and gut and is
major plasma protein;
• in adults, the normal concentration is less than 10 μg/L.
• Increased plasma concentrations of α-fetoprotein are seen in
normal pregnancy.
• also use in the diagnosis of neural tube defects
• hepatocellular carcinomas (HCC) and testicular teratomas
and other germ cell (nonseminoma) carcinoma.
• Immunometric assay, For AFP-L3 anion exchange
chromatography detected fluorometrically.

23. α-Fetoprotein (AFP) CONT’D
• Single polypeptide glycoprotein (4% carbohydrate).
• 70 Kda mol wt.
• One of the major proteins in fetal circulation, but
maximum concentration is about 10% that of albumin.
• Closely related to albumin genetically and structurally.
• Chromosome 4q for both proteins.
• Normal < 10 μg/L
• During pregnancy peaks to about 500 μg/L in 3rd
trimester.
• Also increased in hepatitis and liver cirrhosis (mostly
<200μg/L)

24. α-Fetoprotein ( AFP) CONT’D
• > 1000 μg/L indicative of cancer, except in pregnant
women…although this value is achieved when tumor size is
already large hence, early diagnosis is evaded.
• Very useful for determining prognosis and monitoring
hepatocellular carcinoma.
• Half life of AFP 5 days.
• Combination of AFP and hCG useful in classifying and staging
germ cell tumor.
• Three glycoforms based on reactivity to lectin LCA: AFP-L1, AFP-
L2 and AFP-L3.
• AFP-L3 is additionally fucosylated and is produced by cancer
cells, and may be a more specific marker.

25. B. Carcinoembryonic antigen (CEA)
• This tumour marker is present in elevated concentrations
in the plasma of 60% of patients with colorectal cancer.
• Lung and breast cancer as well.
• more commonly with advanced disease (80-100% if
hepatic metastases are present).
• However, elevated concentrations are also found in a
variety of non-malignant conditions, including liver
disease of various types, pancreatitis and inflammatory
bowel disease, and in some people who smoke heavily.
• Immunometric assay.

26. Carcinoembryonic antigen (CEA) CONT’D
• Single chain glycoprotein with 45-55% carbohydrate.
• Mol wt. 150 - 300 Kda.
• Heterogenous …large family of related cell surface
glycoprotein (up to 36 identified), can be separated by
isoelectric focussing…all located on chromosome 19.
• Useful in monitoring of metastatic colon cancer …also
in monitoring breast, lung, gastric and pancreatic
carcinomas.

27. (CEA) CONT’D
• Normal 3 μg/L for non- smokers and 5 μg/L for smokers.
• Concentration is also method dependent, so should
always be compared using the same method.
• May also be elevated in cirrhosis, pulmonary
emphysema, rectal polyps, benign breast disease and
ulcerative colitis.

28. IV. Carbohydrate markers as tumor marker
- high molecular weight glycoproteins
A. CA 125 :
• a marker for ovarian cancer
• CA125 can be increased in benign conditions
(e.g. endometriosis) and in non-ovarian
malignancies
B. CA 15-3:
• carcinoma of breast

29. More on CA-125
• High mol. Wt. glycoprotein (> 200 KDa) with 24%
carbohydrate content and detected by monoclonal
antibody OC 125.
• Physiological function unknown.
• Expressed by epithelial ovarian tumors and other
tissues (normal or pathologic) of mullerian origin.
• Useful in detecting residual disease in cancer
patients after initial therapy, and also to monitor
response to therapy.

30. V. Blood group antigens as tumor marker
A. CA19-9: -
• adenocarcinoma of pancreas and possibly
colorectal and gastric carcinomas
• Plasma CA19-9 concentrations are elevated in
more than 80% of patients with carcinoma of the
exocrine pancreas
B. CA50: -
• colorectal carcinoma

31. VI. Protein as tumor marker
• Paraproteins are detectable in either serum or
urine in 98-99% of patients with myeloma
• Bence Jones protein can be detected in
Multiple myeloma
• Thyroglobulin – thyroid cancer

32. VII. Genes as Tumor marker
• Mutations in oncogenes and tumour suppressor
genes are commonly detected in cancers
• Activation of proto-oncogenes is found to be
associated with cancer
– Mutation in ras Gene is found in AML,
– Mutation in HER-2/neu is found in breast, ovarian and
GI tumor
• Mutation in tumor suppressor Gene also lead to
cancer
– Retinoblastoma (RB) gene – Retinoblastoma
– P53 Gene – colon carcinoma, breast carcinoma

33. THANKS…