Tumour Markers Ppt By Dr Vijay

TUMOUR MARKERS : AN OVERVIEW Indian Journal of Clinical Biochemistry, 2007 / 22 (2) 17-31 T. Malati Department of Biochemistry, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad- 500 082, India

TUMOUR MARKERS • Synthesized in excess concentration. • Endogenous products or products of newly switched on genes. • Excellent clinical relevance in monitoring • Early detection of cancer

CLASSIFICATION 1.Oncofetal antigens e.g. AFP, CEA, Pancreatic oncofetal antigen, fetal sulfoglycoprotein. 2. Tumor associated antigens /Cancer Antigens e.g. CA125, CA19-9, CA15-3, CA72-4 CA50 etc.

7.Hormones e.g.β-hCG Calcitonin,

4. Hormone receptors

e.g. estrogen and progesterone receptors 5. Enzymes and Isoenzymes -PSA, PAP, NSE, PALP, TDT, Lysozyme, alpha amylase 6. Serum and tissue proteins -β-2microglobulin -GFAP, -protein S-100, -ferritin, -fibrinogen degradation products 7. Other biomolecules e.g. polyamines

An ideal tumor marker should have the following criteria 1.Highly sensitive 2.Highly specific 3.Able to differentiate between neoplastic and nonneoplastic disease 4.Its levels should be preceding the neoplastic process

ALPHA FETOPROTEIN (AFP) • It is expressed either during malignancy or during intra uterine or early postnatal life. • <15 ng/ml. • The clinical significance of AFP - Prenatal diagnosis of open spina bifida, - Anencephaly, - Atresia of esophagus and

THE ROLE OF AFP IN MALIGNANCY Diagnosis, prognosis and monitoring of2.Primary hepatocellular carcinoma 3.Hepatoblastoma, 4.Non-seminomatous testicular germ cell tumors 8.Germ cell tumors of ovary and extragonadal germ cell tumors 10.In malignancies of

•

HUMAN CHORIONIC (βHCG) AGONADOTROPIN 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

CARCINO-EMBYRIONIC ANTIGEN (CEA) • Adenocarcinoma of the digestive organs. • Primary use in the detection of local and metastatic cancer recurrence. • A persistently rising CEA value…. • A declining CEA value…. • Clinical relevance… • Preoperative CEA level has

PROSTATE SPECIFIC ANTIGEN (PSA) • Gammaseminoprotein due to its presence in seminal plasma. • It is a monomer • Prostate epithelium synthesizes PSA • PSA, a neutral serine protease • The 100 KD PSA-ACT complex • PSA-AT (alpha-1 antitrypsin) • PSA-PCI (protease C inhibitor).

PROSTATE ACID PHOSPHATASE (PAP) • 200 times more abundant in prostate tissue than in any other tissue. • Is useful only in staging apparently localized disease i.e., primary prostate cancer before definitive therapy such as radical prostatectomy. • The enzymatic assay appears

TUMOR ASSOCIATED ANTIGENS

CA 125, CA 19.9, CA 15.3, CA 72.4 ETC

CANCER ANTIGEN 125 (CA 125) •Detected by using murine monoclonal antibody OC 125 •Epithelial ovarian carcinoma. •In the serum, milk and

• Levels less than 35 U /ml in serum • Marker of first choice adenocarcinoma ovary. • Higher sensitivity for nonmucinous epithelial ovarian carcinoma. • Breast (17.6%), • 10.4% of benign ovarian tumors. Colorectal (15.1%), Gastric (30.9%), Esophagus (10.5%), Liver (15.1%), Biliary

CA 19-9 (CANCER ANTIGEN 19-9) • Pancreas and gall bladder cancer. • CA-19-9 are highest for the adenocarcinoma pancreas. • Acute and chronic Pancreatitis

CA 19-5 AND CA 50

• Colon, pancreatic and hepatocellularcarcinoma • Individually both antigens have low sensitivity. However use of both together improves

CA 15-3 CA 549

• Associated with breast cancer

CYFRA 21-1 NSCLC such as SCC, adenocarcinoma and large cell carcinomas.

• BETA -2 MICROGLOBULIN (β2M) • B-cell leukemia, lymphomas and multiple Myeloma. Monoclonal

CALCITONIN -Increase in medullary carcinoma of the thyroid, bronchogenic carcinoma, small cell lung cancer, breast, liver, lung, renal cancers TISSUE POLYPEPTIDE ANTIGEN (TPA) • Moderate elevation in many diseases and in pregnancy. • The marked elevation in breast, lung, gastrointestinal, urological, gynecological cancer.

EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) • In SCC, breast cancer, gliomas, lung cancer, blood cancer, and tumors of female genital tract ESTROGEN RECEPTOR (ER), PROGESTERON RECEPTOR (PR) • ER a 70 KD protein is present in nuclei of mammary and uterine tissues • PR is a more sensitive indicator than ER HYDROXY INDOLE ACETIC ACID (5-

FERRITIN •In advanced cancers of breast, ovaries, lungs, colon and esophagus. •In acute myelocytic leukemia, teratoblastoma and SCC of head and neck.

HOMOVANILLIC ACID (HVA) AND VANILYLMANDELIC ACID (VMA) -DETECTING AND MONITORING THERAPY IN PATIENTS OF PHEOCHROMOCYTOMA. -THEIR MEASUREMENTS ARE ALSO

INTERLEUKIN-2 RECEPTOR / TAC ANTIGEN (IL-2R)

• In some types of lymphoid malignancies. • In adult T-cell leukemia TUMOR SUPPRESSOR GENE P53

• Commonly occurring P53 gene mutations are reported in primary breast, colon, ovarian, lung, and esophageal carcinomas.

• LIPIDASSOCIA TED SIALIC ACID IN PLASMA (LASA-P)

• In breast, GIT, lung Ca, leukemia, lymphoma, Hodgkin’s diseases and melanoma. • The slight increase of this marker is also observed in several inflammatory diseases.

• NEURON- • In glucagonomas, insulinomas, carcinoid SPECIFIC tumor, ENOLASE pheochromocytoma, (NSE) medullary carcinoma of the thyroid, oat cell

ALTERATION OF SERUM BETA 2-MICROGLOBULIN IN ORAL CARCINOMA Indian Journal of Clinical Biochemistry, 2002, 17 (2) 104-107 C.R.Wilma Delphine Silvia, D.M. Vasudevan and K. Sudhakar Prabhu. Department of Biochemistry, Kasturba Medical College, Manipal-

ABSTRACT • Serum β2 –microglobulin (β2–m) levels were measured in oral carcinoma patients and compared with normal healthy controls. • It was observed that there was a significant rise in serum β2– microglobulin in oral carcinoma patients.

INTRODUCTION • It was first described by Berggard and Bearn in 1968 • β2 –microglobulin is a low molecular weight, 11600 Dalton protein found on the surface of all cells except erythrocytes. • It was also shown to occur in small quantities in normal human urine, plasma and CSF.

MATERIALS AND METHODS • Patients and controls • Exclusion criteria • Group I: 20 healthy individuals, 8 females and 12 males. • Group II: 4 oral keratosis, 3 males and 1 female. • Group III: 30 oral carcinoma patients, 17

• All patients were clinically staged according to TNM staging system of the International union against cancer (UICC). • This group of patients were further divided into subgroups. Group IIIA: 5 patients with stage I oral cancer. Group IIIB: 7 patients with stage II oral cancer. Group IIIC: 10 patients with stage III oral cancer.

β2 –microglobulin assay

• Serum. • frozen at -70° C until assay. • The serum was analyzed by Enzyme linked immunosorbent assay • 2.4mg/L was used as the upper limit, when 97% of normal values are below this

Statistical analysis • The data were analyzed by using statistical package for social sciences (SPSS) software. • Cases and controls were tested for statistical significance with student’s ‘t’ test. • Values of p<0.05 were considered significant.

RESULTS

• The test showed an abnormal result in only 1 out of 20 of healthy controls and thus the -specificity of 95.2%, - positive predictive value 95%, -negative predictive value of 66.6%, - and efficiency of the test

DISCUSSION • Synthesized and secreted by lymphocytes • It has a low molecular weight and rapid turnover • Elevated levels of β2 –m have been observed in a variety of patients mostly with advanced malignancy and other disease states

• Serum β2 –m values were increased in oral cancer group, when compared with controls, and this is statistically significant (p<0.05) • The mechanism of increase in β2 –m levels in malignancies • It lacks specificity for oral carcinoma as an individual marker because it is elevated