Tumor markers Present; by Dr. Andalib Isfahan Medical School

Overview cancer is a broad term used to describe > 200 different diseases that affect 50 tissues.

What are Tumor Markers？ Biological substances synthesized and released by cancer cells themselves or produced by normal cells in response to tumor. Most tumor markers are proteins

Tumor Specific Transplantation Antigen (TSTA) Tumor antigens Tumor Specific Transplantation Antigen (TSTA) Tumor Specific Antigen (TSA) Viral antigens proto oncogenes Viral Antigen : a- Viral proteins and glycoproteins b- New antigens produced by virally infected host cells under control of viral nucleic acid

Tumor antigens Tumor Associated Antigens (TAA) of certain cancerous tissue BUT large overlap tissue differentiation antigens gene products with increased expression altered glycoproteins and glycolipids Altered expression of gene products Oncofetal antigens Viral Antigen : a- Viral proteins and glycoproteins b- New antigens produced by virally infected host cells under control of viral nucleic acid

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Tumor antigens could be used for Screening of disease. Diagnosis of symptomatic patients. Staging of cancers. Prognostic indicators. Detect recurrence in Follow-Up of disease. Monitoring response to therapy. low sensitivity and lack of specificity and relation to tumor size......limited role in screening The pre-therapeutic level of certain tumor marker can contributes a prognostic factor because of links with... Metabolic activity,Tumor size and Invasion

Tumor marker First tumour marker 1938 Acid phosphatase for metastatic prostate

Tumor markers Are biochemical substances which, as the name suggest, are closely associated with carcinogenesis Are substances, such as proteins, biochemical, or enzymes, produced by tumor cells or by the body cells in response to tumor cells Are substances that can often be detected in higher than normal in the blood, urine, or body tissues of some patients with certain types of cancer Substances present in or produced by a tumor itself or produced by the host in response to a tumor

Tumor markers Measurement of tumor markers: helpful Tumor marker levels could elevated in benign conditions Many tumor markers are not specific to a particular type of cancer In addition diagnosis :help physicians make a plan for appropriate therapy

Tumor markers Used to differentiate tumor from normal tissue Determine presence of tumor based on quantity in blood or secretions Higher quantity in cancer tissue, or in blood from cancer patient, then in benign tumors or normal individuals Few tumor markers are specific for a single type of tumor

Tumor markers Most markers are found in many different types of tumor Monitor a patient response to treatment After treatment :as a part of follow up care to check for recurrence Decrease or return to normal: favorable response to therapy

Tumor marker classification Tumor antigens Enzymes Hormones Oncogene products Oncofetal Receptors Genetic markers

Tumor antigens-Oncofetal Oncofetal:produced during normal emberyogical development and by neoplastic cells Defined by polyclonal or monoclonal antibodies CEA, AFP, HCG

Tumor associated antigens (Cancer antigen)

ENZYMES Neuron specific enolase(NSE) Acid phosphatase Lactic dehydrogenase

Dunn et al. Nature Reviews Immunology 6, 836–848 (November 2006) | doi:10.1038/nri1961

Hormones * Human Chorionic Gonadotrophins (HCG) are secreted in Choriocarcinoma, Ovarian Cancer * Thyroxin is secreted in thyroid cancer

Ideal markers Present in early in disease Before clinical evidence of disease Increase with advancing tumor Decrease with effective therapy Test reproducible Available and cost effective

Ideal marker Specific: produced only by cells of a particular malignancy and not by other cancers, or benign conditions Sensitive: produced in all patient with similar malignancy

Specific organ tumor systems Gastrointestinal tumors CEA AFP CA19-9

Prostate specific antigen PSA Prostate specific antigen

PSA In low concentration in the blood of all adult males Is produced both normal and abnormal prostate cells Elevated PSA levels: in blood of men with benign prostate condition Prostatitis/benign hyperplasia/malignant

PSA PSA level:monitoring the effectiveness of prostate cancer treatment Checking recurrence after treatment

PSA As a screen for prostate cancer or in the elevation of or to follow up a person with prostate disease

Cancer antigen 27-29 For Breast cancer

CA 27-29 Breast cancer Check for recurrence in woman previously treated for stage 2 and stage 3 breast cancer Colon/stomach/kidney/lung/ovary/ pancreas/uterus/liver Nan-cancerous: first trimester pregnancy/endometritis/ovarian cysts/benign breast disease/kidney disease/liver disease

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Neuron-specific enolase Neuroblastoma NSE Neuron-specific enolase Neuroblastoma

NSE Neuroblastoma/small cell lung cancer/wilms tumor/melanoma/cancers of thyroid/kidney/testicule/pancreas Patient prognosis Patient response to treatment

Carcino-Emberyonic Antigen CEA Carcino-Emberyonic Antigen

CEA Oncofetal protein Normal during fetal life(low concentration in healthy adults) Higher concentration in some epithelial malignancies Glycoprotein(molecular weight 200,000KD)

CEA Found on cell membrane Easily released into fluids Related to immunoglobolin super-family genes Normally found in mucus secretions of the stomach, small intestine

CEA Small amount in the blood of healthy people Primary use of CEA: in monitoring colorectal cancer Melanoma/lymphoma/breast/lung/pancreas/stomach/cervix/bladder/kidney/thyroid/liver/ovary Nan-cancerous condition: inflammatory bowel disease/pancreatitis/liver disease Tobacco users

CEA lOW SPECIFICITY and lOW SENSITIVITY

AFP Alpha-fetoprotein

AFP First described oncofetal antigen Normally: by a developing fetus AFP level :elevated :liver cancer/germ cell cancer/ovary/testicule Non-cancerous condition: benign liver condition /cirrohosis or hepatitis/pregnancy

CA 19-9 Cancer antigen 19-9

CA 19-9 A carbohydrated antigen detected by monoclonal antibodies Pancreatic cancer Biliary tract cancer Billary tract disease pancreatitis

TUMOR MARKER Screening Diagnosis Prognosis monitoring

Cancer antigen 125 ovarian cancer

CA 125 Is produced by a variety of cells(ovarian cancer) Is used primarily in the management and treatment of ovarian cancer In woman with ovarian cancer: chemotherapy

CA125 Falling CA125 levels generally indicates that cancer is responding to treatment Increasing CA125 levels during or after treatment: is not responding to therapy

CA 125 To monitor for recurrence of ovarian cancer Uterus/cervix/pancease/liver/colon/breast/lung/digestive tract Non-cancerous condition: elevated CA125(endometriosis/pelvic inflammatory disease/peritonitis/liver disease Menstruation and pregnancy

Human chorionic gonadotropine HCG Human chorionic gonadotropine

HCG Is produced by placenta during pregnancy For screen choriocarcinoma Monitoring the treatment of trophoblastic disease Elevated HCG level:testis/ovary/liver/stomach/pancreas/ lung/pregnancy/marijuana

Cancer antigen 15-3 breast cancer

CA 15-3 In following the course of treatment in women diagnosis with breast cancer(advance) Early stage breast cancer Ovary/lung/prostate Non-cancerous condition: benign breast/ovarian disease /endometrisis/pelvic inflammatory disease/hepatitis Pregnancy

Tumor marker Screen and diagnose cancer Predicting prognosis Monitor treatment observation for cancer recurrence

Realty No marker to date satisfy these criteria

Thank you