The first tumor marker reported was BENCE JONES PROTEIN in multiple myeloma in 1847

1. Tapeshwar Yadav
(Lecturer)
BMLT, DNHE,
M.Sc. Medical Biochemistry
TUMOR
MARKERS

2. Definition
 A tumor marker is a substance produced by
tumor or by a host in response to a tumor,
 used to differentiate a tumor from normal tissue
or
 to determine the presence of a tumor based on
measurements in blood & secretions

3.  The first tumor marker reported
was BENCE JONES PROTEIN in
multiple myeloma in 1847

4.  2end era of TM (1928-1963)
hormones,enzymes,isoenzymes,&proteins
 3rd era of TM(1928-1963)
AFP,CEA
 4th era of TM(1975)
CA-125,CA 15-3&CA 27.29

5. CLINICAL APPLICATIONS
 Screening for cancer
 Diagnosing cancer
 Evaluating cancer prognosis
 Prediction of therapeutic response
 Tumor staging
 Detecting tumor recurrence
 Localising tumor&directing radiotherapeutic
agents
 Monitoring effectiveness of cancer therapy

6. CLASSIFICATION
 ENZYMES
 HORMONES
 ONCOFETAL ANTIGENS
 CYTOKERATINS
 CARBOHYDRATE MARKERS
 BLOOD GROUP ANTIGENS
 PROTEINS
 RECEPTORS
 GENETIC MARKERS

7. Alkaline phosphatase
 Liver ,bone,placenta
 Primary or secondary liver cancer
 Metastatic cancer with bone or liver
 PALP –trophoblast-sera of pregnant women
 Regan isoenzyme
 PLAP-ovarian, lung,trophoblastic GI
cancers,seminoma,Hodgkins disease

8. Creatine kinase
 Dimer –M&B
 CK1-BB-brain ,prostate,git,lung,bladder,uterus
 CK2-MB-Cardiac muscle
 CK3-BB-skeletal &cardiac muscle
 Ck1-prostate cancer;SCLC;

9. LACTATE DEHYDROGENASE
 NON SPECIFIC
 LDH-liver,seminoma,neuroblastoma,non
Hodgkins lymphoma,acute leukemia

10. NEURON SPECIFIC ENOLASE
 Neuronal tissue,neroendocrine tissue
 APUD tissue
 NSE-SCLC,neuroblastoma,pheochromocytoma
 carcinoid,medullary carcinoma of thyroid
 High levels-poor prognosis
 RIA-

11.  UROKINASE -PLASMINOGEN ACTIVATOR
SYSTEM-
BREAST &COLORECTAL CANCER
CATHEPSINS-BREAST CANCER
MATRIX METALLO PROTEINASES-
MMP-2 IN OVARIAN TUMOR CELLS

12. Hormones
 ACTH-cushings syndrome,SCLC
 ADH-SCLC,adrenal cortex,pancreatic
 Bombesin –SCLC
 Calcitonin –medullary thyroid
 Gastrin-glucagonoma
 GH-pituatary adenoma,renal,lung
 HCG-embryonal,choriocarcinoma,testicular
 HPL-trophoblastic,gonad,lung

13. Hormones
 NEUROPHYSINS-lung(SCC)
 PTH-liver,renal,breast,lung
 PROLACTIN-pituitary adenoma,renal,lung
 VIP-pancreas,bronchogenic,
pheochromocytoma,neuroblastoma
ACTH-cushings syndrome,lung cancer(small cell)
Calcitonin –familial medullary carcinoma thyroid
RIA

14. ONCOFETAL ANTIGENS
 PROTEINS –fetal life
 High conc in sera of fetus;
 Disappear after birth
 Cancer pts-reappears
 Immunometric assays

15. ONCOFETAL ANTIGENS
 AFP-Hepatocellular,germ cell
 β-oncofetal antigen-colon
 Carcinofetal ferritin-liver
 Pancreatic oncofetal-pancreas
 Squamous cell antigen-cervical,lung,skin
 Tennessee antigen-colon,GI,bladder

16. Cytokeratins
 Proteins of cytoskeletal intermediate filaments
 Type 1-smaller & acidic
 Type 2-larger &neutral to basic
 Immuno radiometric assay

17. Cytokeratins
 TISSUE POLYPEPTIDE ANTIGEN-pregnancy;
differentiating cholangiocarcinomas from HCC
 TISSUE POLYPEPTIDE SPECIFIC ANTIGEN-
LUNG
CYTOKERATIN 19 FRAGMENTS-
CYFRA 21-1-SCC,non small cell lung cancer
SQUAMOUS CELL CARCINOMA ANTIGEN

18. Carbohydrate markers
 Antigens on the tumor cell surface or
 Secreted by tumor cells
 More specific
 High mol wt mucins or blood group antigens
 Immuno radiometric assay

19. CARBOHYDRATE MARKERS
 CA-125-ovarian,endometrial
 CA 15-3-Breast,ovarian
 CA 549-Breast,ovarian
 CA 27.29-Breast

20. Blood group antigens
 Blood group carbohydrates identified by
monoclonal antibodies
 Immunoradiometric assay

21. Blood group antigens
 CA 19-9- Pancreatic,GI,hepatic
 CA 19-5-GI,pancreatic,ovarian
 CA 50-pancreatic,GI
 CA 72-4-Ovarian,breast,GI
 CA 242-GI,pancreatic

22. proteins
 Tumor markers that are not enzymes,hormones
or high in carbohydrate content.
 S-100 proteins-19 related ca binding proteins
 Diagnostic histological marker of melanoma &
melanoma metastasis
 Thyroglobulin—differentiated thyroid cancer
 IMA &RIA

23. PROTEINS
 Β2 Microglobulin-Multiple myeloma
B-cell lymphoma,CLL,
Waldenstrom macroglobulinemia
.C-peptide-Insulinoma
.Ferritin-liver ,lung,breast,leukemia
.Immunoglobulin-Multiple myeloma,Lymphoma
.Pancreas associated antigen-pancreas,stomach
.Tumor associated trypsin inhibitor-lung,GI

24. Receptors
 Estrogen & progesterone receptors-
In Breast cancer
Indicators of hormonal therapy
prognosis
 EGFR-head&neck,ovarian,cervical,bladder,
oesophagial
 IMMUNOCYTOCHEMICAL ASSAYS

25. Chromogranins
 Cg A,B
 Secretogranin 2,3,4&5
 Found in neuroendocrine cells
 Its wide distribution &co-secretion make it an
excellent histochemical &plasma marker of
neuroendocrine tumors
eg:carcinoid tumors
neuroblastoma,pheochromocytoma
IMMUNO ASSAY

26. GENETIC MARKERS
 Oncogenes-
 Activation of proto oncogenes-cancer
 Suppressor genes-
 Loss of gene-deletion or monosomy-cancer
 IMMUNOHISTOCHEMISTRY

27. Genetic markers
 ONCOGENES
ras Genes-leukemias,lymphomas
c-myc Gene-leukemias,lymphomas,SCLC,
Her-2/neu(c-erbB-2)-breast,ovarian,GI
bcl-2-lymphomas,myelomas,leukemias
BCR-ABL Gene-CML
RET-Papillary thyroid cancer

28. Tumor suppressor genes
 RETINOBLASTOMA GENE-RB
 P53 Gene-colorectal,breast,lung
 APC-colon
 NEUROFIBROMATOSIS TYPE 1(NF 1)
von Recklinghausen disease
 BRCA 1&BRCA 2-Breast,ovarian
 DCC GENE-Colon

29. Miscellaneous markers
 Cell free nucleic acids-circulating DNA &RNA
 Circulating cancer cells

30. PROSTATE SPECIFIC ANTIGEN
 Gammaseminoprotein due to its presence in
seminal plasma.
 It is a monomer
 Epithelial cells of acini&ducts of prostate
 PSA, a neutral serine protease
 PSA-ACT or AMG
 SCREEN ,STAGE&MONITOR TREATMENT&
RECURRENCE OF PROSTATE CANCER
 IMMUNOASSAY&ULTRA SENSITIVE ASSAY

31. PROSTATIC ACID
PHOSPHATASE
 200 times more abundant in prostate tissue
than in any other tissue.
 Not sensitive as PSA for screening or
detection of early cancer
 Is useful only in staging apparently localized
disease i.e., primary prostate cancer before
definitive therapy such as radical
prostatectomy.
 The enzymatic assay appears superior to the
immunoassay

32. ALPHA FETOPROTEIN (AFP)
 It is expressed either during malignancy or
during intra uterine or early postnatal life.
 <10 μg/ml.
 The clinical significance of AFP
- Prenatal diagnosis of open spina bifida,
- Anencephaly,
- Atresia of esophagus and
- Multiple pregnancy.
IMMUNOASSAY

33. THE ROLE OF AFP IN
MALIGNANCY
Diagnosis, prognosis and monitoring of-
1. Primary hepatocellular carcinoma
2. Hepatoblastoma,
3. Non-seminomatous testicular germ cell
tumors
4. Germ cell tumors of ovary and extragonadal
germ cell tumors
5. In malignancies of gastrointestinal tract,
pancreas, lungs, kidney, and breast etc

34. CARCINO-EMBRYOGENIC
ANTIGEN
 Colorectal ,GI,lung,&breast carcinoma
 Primary use in the detection of local and
metastatic cancer recurrence.
 A persistently elevated CEA –colon cancer
 CEA declines-after successful initial therapy
 CEA stable-remission
. Rising CEA –recurrence of disease
 Preoperative CEA level has prognostic
significance.
 IMMUNOMETRIC ASSAY

35. HUMAN CHORIONIC
GONADOTROPIN
β-HCG
 A 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
IMMUNOMETRIC ASSAY

36. CANCER ANTIGEN 125 (CA 125)
Detected by using murine monoclonal
antibody OC 125
 Ovarian,endometrial carcinoma.
 In detection of reccurent metastasis use of
CA125 as indicator is 75% accurate

37. Squamous cell carcinoma
antigen
 SCCA is elevated In variety of SCC of
cervix,lung,skin,head,neck,digestive tract,ovaries
&urogenital tract

38. TISSUE POLYPEPTIDE ANTIGEN
(TPA)
 Moderate elevation in many diseases and in
pregnancy.
 The marked elevation in breast, lung,
gastrointestinal, urological, gynecological
cancer.
 Sensitive but nonspecific tumor marker

39. ANALYSIS
 ENZYME ASSAY
 IMMUNOASSAY
 RECEPTOR ASSAY
 MASS SPECTROMETRY INTERFACED WITH
LIQUID OR GAS CHROMATOGRAPHS
 MICROARRAYS

40. 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
5. It should be easily assayable

41. Thank you for your attention!