Tumor Markers Test Questions Flashcard

Tumor
new growth of tissue forming an abnormal mass, often called a neoplasm. CAuse is usually unknown.
Malignant
unregulated growth and cancerous, capable of invading ajacent tissues as well as spreading to distant tissues.
Benign
A timor that does not grow in an unlimited aggressive manner and does not invade. Not cancerous.
Cancer
disease state involving uncontrolled growth of cells derived from normal tissue. Early detection offers the best chance for cure, cure is to remove the tumor.
Metastasis
aggressive spread of cancer from it’s primary site to other places in the body. Divided into phases.
Phases of Metastasis
1) Tumor at the primary penetrates the adjacent surrondings and eventually reaches a blood or lymph vessel.
2)Tumor enters the blood or lymp vessels and are carried to distant sites.
3)tumor anchors in the capillary beds or the solid tissue of a distant organ
4)tumor cells penetrate the vascular walls and abnormally grow at the new site.
Remission
absence of a disease in a patient with the possibility of the disease returning.
Biopsy
a representative tissue sample taken for microscopic examination. Used to establish or rule out a Dx of cancer.
Tumor Marker
biochemical molecule found in or produced by a tumor. Used to differentiate a tumor from normal tissue or to determine the presence of a tumor.
How are tumor markers used for screening?
screening a healthy or high risk population for the presence of cancer.
assisting with the general dx of cancer or identifying a specific type.
monitoring before during and after treatment.
Why are tumor markers of limited value?
lack sufficent specificity to any organ system.
inadequate sensitivity means that the disease is probably too advanced by the time markers elevate.
increases can occur due to nonmalignant reasons.
What is tumor staging used for?
evaulate relative merits of different treatment regimens and survival rates. Also eases the exchange of information among cancer treatment centers.
What are the 5 stages of tumors?
0 only in the layer of cells in which it began
I, II, III higher number idicates more extenses disease and/or spread to adjacent organs or lyph nodes.
IV cancer has spread to another organ
How are Tumor Markers used to evualte success of initial treatment?
Successful therapy should cause a decrease in concetration of tumor markers.
Increase suggests progression.
A rise or reappearance of a tumor marker concentration indicates recurrence.
How are tumor markers a prognostic idicator?
Predicts the likely outcome for a patient. A tumor that produces a specific marker may indicate a poor prognosis.
Oncofetal Antigens
exist in both fetal tissue and cancer cells, very non-specific to cancer types or other disease states. Common ones are : AFP (Alpha Fetoprotein)& CEA (Carcinoembryonic Antigen)
Hormones
can secrete excessive amounts, may be produced at a distant site by a non endocrine tissue (ectopic syndrome) Commonly used: B-hCG (BEta-human Chorionic Gonadotropin)
Carbohydrate Antigens (CA)
high weight molecular weight glycoproteins, not specific, support monitoring rather than screening or Diagonosis. Commonly used – CA-125 & CA-15-3
Enzymes
Released into the blood circulation as the result of tumor necrosis or cahnge in the permeability of the cell, not unique for a specific organ. Elevated levels may indicate malignancy. Commonly used: PSA (Prostatic Specific Antigen)
CA-15-3
Carbohydrate Antigen, used to monitor breast cancer patients after mastectomy.
HER 2-neu
WORST PROGNOSIS..bound protein receptor elevated in 25-35% of breast cancers. Frewuent in breast, ovarian, and stomach cancer. Associated with disease recurrence.
5-Hydroxyindoleacetic acid (5-HIAA)
metabolite of serotonin. Overexpressed in cancer of the small intestine.
Vanillylmandelic Acid (VMA)
metabolite of Catecholamine hormones. Over exressed in tumors of the adrenal glands.
AFP (Alpha Fetoprotein)
oncofetal antigen, indicates a primary hepatocellular tumor or a germ cell tumor of the testicle or ovary. reaches peak fetal concentration of 300ng/mL at 12 weeks. Reaches traces amounts 18 months after birth.
Abnormal Serum/Plasma Elevations of AFP
Most Widely a marker for hepatocellylar carcinoma and testicular cancer. Also assocaited with ovarian cancer.
Transiently elevated during pregnancy and benign liver disease.
Directly Proportional to size of tumor.
Clinical Values of AFP
Upper limit in adults is 15ng/mL
Newborns and infants have much high levels.
Multiple measurements are used to monitor treatment.
CEA (Carcinoemryonic Antigen)
oncofetal antigen most commonly associated with cancer of the colon. glycoprotein found in the fetal digestive system and liver. Useful in aid of Dx of cancer and monitoring after treatment.
Abnormal Plasma Elevations of CEA
more often seen in patients with maetastatic diseases, colon cancer is the msot prevalent. Lacks specficity and sensitivity, not a screening tool. Benign disorders such as cirrhosis, emphysema, rectal polyos breast diseaase, ulcerative colitis.
Prognostic Indicator of CEA
tendency to metastasize earlier, aggressively invade, shorter remission time. CEA enhances invasion and metastases.
B-hCG (beta Human Chorionic Gonadotropin)
Hormone tumor marker for cancer of the testis or ovary, glycoprotein normally secreted by the placenta, immunogenically specific and distinct rom any other protein.
Abnormal Elevations of B-hCG
throphoblastic tumors, germ cell tumors of the ovary and testes, lover elevations have been reported in skin cancer, cancer of the breast, gastrointestinal tract, and lung.
B-hCG used for treatment monitoring
increasing B-hCG correlates with the size of the tumor. >400,000 IU/L is high risk for treatment failure. Should decrease after surgery or treatment. Annual measurement reccomeneded to detect relapse.
CA-125 (carbohydrate antigen 125)
marker for ovarian and endometrial carcinomas. produced by ovarian cancer cells, lower levels in the normal tissues of female reporodcutive tract.
Abnormal levels of Ca-125
50% of Stage I ovarian cancer
90% of Stage II
>90% of Stage III & IV
Increasing levels correlate with timor size.
CA-125 used to monitor treatment
falling CA-125 level indicates response to treatment.
Serial measurements post treatment detect remaining recurrent cancer, correlate in 80-90% of cases.
A 10 fold decrease in the CA-125 level after 1 cycle of treatment indicates improvement. PErsistent elveation after 3 is a poor prognosis.
PSA (prostate Specific Antigen)
organ specific enzymatic tumor marker, differentiates prostate cancer from other benign conditions. Used to detect, stage and monitor treatement.
Abnormal levels of PSA
benign prostate hyperplasia
prostatitis
PRostate infarction.
MOST USEFUL TUMOR MARKER FOR PROSTATE CANCER.
Monitoring Treatment with PSA
monitor the success of prostatectomy, radiation, and dectection of reocurrence. measureable PSA after prostatectome indicates metasiss or residual tissue. Used as a screening tool in combo with DRE
Enzyme-Immunassay (EIA)
most common method used to detect tumor markers.
Immunocytochemical
biopsies and cytologic specimens. Often used to detect HER 2-neu over expression in breast cancer.
Immunoradiometric (IRMA)
done occassionally on serum.
Antibodies (Ab)
produced by the immune systems of higher animals. produced by specific white blood cells as a response to foreign substances.
Light Chains
small polypeptide subunit of antibody. Two domains: one varriable (determines Ag binding site) and one constant.
Heavy Chains
Large polypeptide subunit of protein complex. Determines the class of Ab. Two domains present: one variable (determines Ag binding site, and three constant.
Fragment Antigen Binding (fab fragments)
region of antibody that binds to antigens. composed of one constant and one variable domain of each heavy and light chain. determines shape and thus specificity of the Ag binding site.
Fragment Crystallization Portion (Fc fragment)
Tail region of Ab that interacts with cell surface receptors. Two identical protein fragments derived from two constant regions of heavy chains.
Disulfide Bonds (s-S bridges)
covalent bond between the sulfhydrl groups of two cystine amino acids. stabilizes the protein structure.
What are the 5 classes of Immunoglobulins?
IgM, IgG, IgA, IgE, IgD.
IgM
predominant Ig in initaul Immune response, can bind up to 10 antigens, accounts for 6% of total Ig. Pentamer.
IgG
major serum Ig (80%). Responsible for defense of newborns.. only Ig that crosses placenta. Primary Ab of the secondary immune response. Monomer.
IgA
Predominant Ig in body secertions. First line of defense against local infections. 13% of serum Igs, Polymeric usually a Dimer.
IgE
Trace amoints on the surface of mast cells. responsible for manifestation of allergy and other immediate hypersensitiy reactions. Monomer.
IgD
Function is unclear compared to other Igs, found of the surface of lymphocyte memranes involved in Ag recognition, accounts for 1% of serum Ig. Monomer.
Monoclonal Antibodies
Homogeneous antibodies derived from the same cell line of B lymphocytes. Produced in a laboratory and used commercially because each monoclonal Ab will bind the same epitope. (antigen)
Polyclonal Antibodies
Heterogeneous Antibodies dervied from many different ab-producing B lymphocytes that recognize the same Ag, but different epitopes on the same Ag.
Antigen-Antibody Binding
Structural Specificity. Key and lock method. Shape of epitope matches shape of Ab binding site. Binding Site is determined by Variable Domains. Non covalent and thus Irreversible.
Label
a reagent that is tagged with some component that allows a detection or visualization
Common enzyme labels
horseradish peroxidase, alkaline phosphatase, Glucose-6-phosphate dehydrogenase (g6PD)
Label
a reagent that is tagged with some component that allows a detection or visualization
Fluorescein
organic dye that absorbs blue light emits a yellow green fluorescence. MOST WIDELY USED FLUOORESCENT LABEL.
Rhodamine
Organic dye. absorbs yellow light. emits deep red fluorescence. longer wavelength than fluorescein.
Luminescent Labels
OFten luminol or acridium esters, requires an enzyme.
Type 1 Immunoassay
single site, heterogenous, noncompetitive immunoassay (IA)I.E. Immunofixation Electrophoresis (IFE)
Type 1 IA process
1)Ab of known antigenicity is tagged witha label.
2)Ab is mixed with a patient Ag. Ab will bind epitopes on Ag
3) Excess or unbodun Ab is washed away.
4) Remaining Ab is measured. Directly proportional to amount of Ag present.
Type 2 Immunoassay
two site, heterogenous, noncompetitive immunoassay. i.e. Enzyme linked immunosorbant Assay (ELISA)
Type 2 IA Process
1) Uses 2 Ab-Ag reactions. (2Ab, 1Ag)
2) Ab of known specificity is attaced to a solid phase
3)PAtient Ag is added- epitopes on Ag specific will bind. unbound will wash off.
4) Second labeled Ab is introduced. Ab will bind specific epitopes on Ag, excess is washed away.
5) label is measured. amount of Ab label is directly proportional to amount of Ag.
Type III Immuno assay
competitive, homogenous Immunoassay, I.e. Enzyme multiplied immunoassay Technique (EMIT) Flourescence Polarization Immunoassay (FPIA)
Type III IA process
1) Pt Ag and REagent labeled Ag are introudced at the same time. Ab is limited amounts. Pt Ag and REagent Ag compete for limited binding sites.
2) Binding of Reagent Ag to Ab inactivates label.
3) Free Reagent Ag is measured
4) amount of free reagent Ag is directly proprtional to the amount of patient Ag that has been bound to Ab.
Type IV IA
competivie heterogeneous IA, I.E, Chemilumiescense, Nephelometry, Turbidometry.
Type IV IA process
similar to type III
1) Pt and a reagent labeled Ag compete for limited Ab binding sites.
Ag label remains active when bound to Ab,
free and bound reagent ag must be separed before measuring. Free or bound may be bured. realted to PT Ag present.
Prozone of immunoprecipitation reactions
Ab excess zone, limited Ag, mixtures of Ab and Ag do not precipitate visibly because of excess Ab.
Zone of Equivalence
Equivalent concentration of Ab and Ag. Optimal conditions for immunoprecipitation reactions.
Postzone
Excess Ag, limited Ab.
Immunoprecipitation Technique
Precipitating an Ag out of a solution by binding it to antibodies.
Ag an Ab recognize each other and complex. Complex can get large enough to form a precipitate. Bsis for agglutination assays.
Western Blot
proteins are separated by gel electrophoresis, transferred to a membrane and identified through labeld Abs. Not routinely used in clinical lab. except for specific proteins. Confirmation of HIV.
Chemiluminescence
Technique based on quantitation of an analyte based on emission of light resulting from a chemical reaction.
Chemiluminescence Procedure
1) fixed amounts of enzume lamed Ag competes with unlabeled Ag for a limited number of Ab binding sites.
2) Label is not inactivated by binding to Ab
3) Upon separation of free and ubound reagent antigen substrate is added and ezyme product measured.
Interpreted with a luminometer. amount of light inversely proportional to amount of analyte present.
Direct and Indirect Immunofluorescence Analysis
Abs not only react with specific Ags but can themselves be Ags. Used extensively in the detection of auto-antibodies.
Direct and Indirect Immunoflyorescence analysis procedure
1)Ag source to the specific Ab being tested is affixed to a solid surface
2) Pts serum is diluted and place on slide to cover Ag source
3) Ab present in serum will bind to specific Ag
4) Unbound Ab is washed away.
5) Anti-human Ig is conjaged to a substace that will fluorescence when exposed to a specific Wl
6) conjagated marker for Ab will bind to Ab.
Often used in cytotechnology and histotechnology.
Turbidiometry
measurement of light transmitted through a suspension of particles which can be measured by a spectrophotometer
Turbidiometry procedure
Absorbance measurements are made at 180 degress to the incoming light.
Turbidity of sample causes decrease in the intensity of light beam.
Nephelometry
direct measurement of light scattered by particles suspended in solution. Detects scattered light at 90 degress from the light source. Sensitive to low levels of Ag-Ab concentrations.

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