Tumor Markers HL.pptx PDF

TUMOR MARKERS  OBJECTIVES Upon completion of lecture and assigned reading, the student will be able to accomplish the following objectives: 1. Define the following terms: Tumor, Benign tumor, malignant tumor, Cancer and Tumor marker. (C-1) 2. List the characteristics of an ideal tumor marker....

TUMOR MARKERS  OBJECTIVES Upon completion of lecture and assigned reading, the student will be able to accomplish the following objectives: 1. Define the following terms: Tumor, Benign tumor, malignant tumor, Cancer and Tumor marker. (C-1) 2. List the characteristics of an ideal tumor marker. (C-1) 3. List the clinical uses of tumor markers? (C-1) 4. Contrast screening test for cancer vs. confirmatory test for monitoring success of treatment. (C-2) 5. List the different types of tumor markers? (C-1) OBJECTIVES 6. Evaluate the clinical significance of the following tumor markers: CEA, AFP, PSA, HCG, CA 15-3, CA 27-29, CA 19-9, and CA 125. (C-3) 7. Differentiate between Prostate cancer and Benign Prostatic Hyperplasia using laboratory results. (C-2) 8. Given a case study, evaluate the laboratory results and patient symptoms related to tumors. (C-3) DEFINITIONS  Tumor or neoplasm Abnormal/uncontrolled proliferation of cells.  Benign tumor Tumor that remains confined to its primary site.  Malignant tumor Tumor that is capable of invading surrounding normal tissue and metastasizing (spreading) through the circulatory and lymphatic systems to distant body sites—also called “Cancer”.  Cancer a malignant neoplasm or tumor DEFINITIONS  Tumor marker a substance synthesized by the tumor or by the host in response to a tumor that can be used to detect the presence of the tumor  Anaplasia refers to loss of cell differentiation and change in cell and tissue structure from typical or normal.  Carcinoma is a malignant growth arising from skin or organ tissue epithelium  Adenoma is a benign growth arising from glandular epithelium. DESIRABLE CHARACTERISTICS OF A TUMOR MARKER  Specific for cancer  Always present with tumor  Amount of marker produced should correlate well with the tumor load  The half-life of the marker should be short so serum levels must drop producing undetectable concentrations when patient is in remission.  Levels of marker should have prognostic value DESIRABLE CHARACTERISTICS OF A TUMOR MARKER  Screening tests identify individuals in the early stages of disease in the asymptomatic population.  Screening tests should have high diagnostic sensitivity; that is the test should have a low rate of false negative results.  Confirmatory tests to a positive screening test should have high diagnostic specificity; that is the test should have a low rate of false positives  Assay for the marker should be analytically sensitive, specific, accurate, precise, easy to perform, inexpensive, and rapid. USES OF TUMOR MARKERS  Screening for disease  Diagnosis for symptomatic patients  Aid in clinical staging  Measurement of tumor burden  Monitoring response to therapy  Detecting recurrence of disease  Prognostic indicator TYPES OF TUMOR MARKERS  Enzymes and isoenzymes  Hormones, neurotransmitters and their metabolites  Receptors (estrogen, progesterone, androgens, corticosteroids)  Proteins (immunoglobulins, glycoproteins, carcinoembryonic proteins or oncofetal antigens)  Genetic markers (Oncogens and supressor genes)  Other markers (amino acids) CARCINOEMBRYONIC ANTIGEN (CEA)  Belongs to the family of glycoproteins  Elevated in:  Colon cancer  Lung cancer  Gastric cancer  Breast cancer  Pancreatic cancer  Ovarian cancer  Uterine cancer  Prostate cancer CEA  Problems with using CEA as a marker:  Elevated in non malignant conditions such as pulmonary emphysema, acute ulcerative colitis, alcoholic cirrhosis, inflammation of the bowel, cystic fibrosis, etc.  Not specific, therefore has no diagnostic utility  Most useful in establishing prognosis and monitoring therapy and reoccurrence of disease PROSTATE SPECIFIC ANTIGEN (PSA)  Serine protease produced exclusively by the epithelial cells in the prostate.  PSA is the only tissue-specific marker identified so far, but is not specific for prostate cancer.  Found in small amount in normal prostate  Also elevated in Benign Prostatic Hyperplasia (BHP)  Only tumor marker approved for screening for prostate cancer and is a useful diagnostic tool.  Useful in detecting, staging and monitoring disease.  Serum PSA is roughly proportional to tumor volume and should return to normal within one month of prostectomy. PSA  PSA exists in both free and complex (PSA complexed to alpha1-antichymotrypsin)form in serum.  Immunoassays are available for total, free and complex PSA  % free to total PSA and % complex to total PSA are used to differentiate b/w Prostate cancer and BPH.  It is imperative that the same assay be consistently used to monitor PSA values for a patient due to different cut-offs for different assays HUMAN CHORIONIC GONADOTROPIN (HCG)  Pregnancy associated hormone, normally secreted by the synctiotrophoblastic cells of the placenta.  Dimer composed of alpha and beta subunits  Alpha subunit is found in FSH, LH, and TSH  Beta subunit is specific to HCG  HCG is commonly measured to confirm pregnancy but is also extensively used to monitor trophoblastic pathologies and germ cell tumors of the testes and ovaries. ALPHA-FETOPROTEIN (AFP)  Synthesized in the yolk sac, fetal liver, GI tract and kidney  Structurally related to Albumin  Used as a marker for neural tube defects and a screening tool for down syndrome  Moderate elevations in liver disease (hepatitis / cirrhosis)  AFP levels differentiate benign from malignant conditions CANCER ANTIGEN 15-3  Glycoprotein present on mammary epithelium  Increased in breast cancer but not specific  Increased in a variety of carcinoma (pancreatic, lung, ovarian, colorectal and liver)  Used to monitor patients after surgery  Used in combination with CA 27-29 (FDA approved for monitoring recurrence) and other breast cancer markers CA 125  Glycoprotein defined by monoclonal antibody OC125  Good marker for ovarian cancer but not specific  Limited use in diagnosis but useful in conjunction with CEA  Useful in monitoring disease in ovarian cancer patients CA 19-9  Blood group antigen  Specific for pancreatic cancer but also present in other gastrointestinal cancers  May also be increased in diseases associated with biliary tract obstruction and cystic fibrosis  Used to monitor therapy and predict recurrence ENZYMES/ISOENZYMES AS TUMOR MARKERS  Prostatic acid phosphatase (PAP) is used as a tumor marker for prostate cancer  CK-BB is used as a tumor marker in prostate and stomach cancer  ALP is used as a tumor marker of bone and liver  Amylase and Lipase are tumor markers for pancreatic cancer CASE STUDY  A 59 year old patient presented with symptoms of low back pain, difficulty with urination and urinary urgency. Upon physical examination, the physician palpated a small hard nodule in his prostate. Initial lab values included the following: Calcium 10.0 mg/dL (8.5 – 10.4) Protein 7.4 g/dL Albumin 4.1 g/dL ALP 102 U/L PAP 2.3 ng/mL (