Proteins and Tumor Markers
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What are tumor markers used for?
- Tumor staging
- (not very useful in diagnosis)
Name the ideal characteristics of a tumor marker
- Measured easily
- High analytical sensitivity of assay method
- High analytical specificity of assay method
- Cost effective
- Test result contribute to patient care and outcome
Where is the prostate specific antigen (PSA)?
Produced by the epithelial cells of the prostate gland
What form of PSA in the blood would lack immunoreactivity?
PSA enveloped by protease inhibitor, alpha2-macroglobulin
What form of PSA found in the blood is immunologically detectable - but complexed?
Complexed to another protease inhibitor, alpha1-antichymotrypsin
What form of PSA found in blood is immunogically detectable - but free?
Free PSA is NOT complexed to a protease inhibitor
Describe the specificity of PSA
- PSA is a tissue specific marker but NOT tumor specific
- Small amounts are present in the serum normally
- Lacks specificity because serum PSA is increased in benign protstate hypertrophy as well as in adenocarcinoma of the prostate
When is a biopsy of the prostate recommended?
- PSA >2.5 ng/mL
- Rise in PSA >0.75 ng/mL/year - even if <2.5 ng/mL
What PSA test is associated with a higher risk of prostate cancer?
Lower % Free PSA is associated with higher risk of prostate cancer
What mehodologies are used to measure PSA?
- Fluorescence immunoassay
- Enzyme immunoassay
- Chemiluminescence immunoassay
What tumor marker is the oncofetal glycoprotein antigen and synthesized in the liver, yolk sac, and GI tract of the fetus?
What is the reference range of AFP?
Adult <20 ng/mL
What causes an increase in AFP, in a nonpregnant person?
- Hepatocellular carcinoma
- Testicular and ovarian teratocarcinomas
- Pancreatic carcinoma
- Gastric and colonic carcinomas
- Nonmalignant disorders (Hepatitis and Chronic active hepatitis)
What is AFP also used for, other than a tumor marker?
To monitor therapeutic response of cancer patients to treatment protocols
What causes AFP to increase in a pregnant person?
- Spina bifida
- Neural tube defects
- Fetal distress
What causes AFP to decrease in a pregnant person?
What tumor marker is an oncofetal glycoprotein antigen and normally found in epithelial cells of the fetal GI tract?
Carcinoembryonic antigen (CEA)
What causes an increase in CEA?
- Adenocarcinoma of digestive tract
- Colorectal carcinoma
- Other malignancies
- Noncancerous disorders
What is CEA also used for, other than a tumor marker?
Monitoring therapeutic response of cancer patients to treatment protocols
What tumor markers can also be used to monitor therapeutic response of cancer patients to treatment protocols?
What tumor marker is a glycoprotein that is composed of alpha and beta-subunits?
hCG (human chorionic gonadotropin)
What normally secretes hCG?
Trophoblast cells of the placenta
What subunit is unique to hCG?
What causes an increase in hCG?
- Trophoblastic tumors
- Nonseminomatous testicular tumors
- Ovarian tumors
What tumor marker is a mucin glycoprotein antigen and useful for monitoring therapeutic response and detecting recurrence of breast cancer in patients previously treated?
What causes an increase in CA 15-3?
- Chronic hepatitis
- Systemic lupus erythematosus
What tumor marker is a mucin glycoprotein antigen and a marker for ovarian and endometrial cancer?
What tumor marker is a glycolipid blood group antigen-related marker, a derivative of the Lewis blood group Lexa, and a marker for pancreatic, colorectal, lung, and gastric carcinomas?
Name the test methods used for quantification of 24 hour urinary protein
What is the reference range for urine total protein (random and 24 hour)?
- Random - 1-14 mg/dL
- 24 Hour - <100 mg/day
What causes an increase in urine protein?
- Tubular or glomerular dysfunction
- Multiple Myeloma
- Waldenstrom macroglobulinemia
- Nephrotic syndrome
What protein may be found in the urine of patients with multiple myeloma?
Bence Jones protein
What can cause the glomerular membrane to be damaged?
- Collagen disease
Glomerular dysfunction can be detected in its early stages by measuring what in the urine?
What is a condition where the quantity of albumin in the urine is greater than normal, yet it is not able to be detected by the urine dipstick method?
The presence of microalbumin in a diabetic individual is a concern because it ___________
Generally precedes nephropathy
What are the methods for the quantification of microalbumin?
- Enzyme immunoassays
- Immunonephelometric assays
What is the reference range of urine albumin?
What is CSF and where is it formed?
- Ultrafiltrate of plasma
- Formed in the ventricles of the brain
Name the test methods used for CSF
What is the reference range for CSF protein?
What causes an increase in CSF protein?
- Viral, bacterial, and fungal meningitis
- Traumatic tap
- Multiple sclerosis
- Herniated disk
- Cerebral infarction
What causes a decrease in CSF protein?
- CNS leakage of CSF
What methodology is based on the change in velocity of light (light is bent) as light passes through the boundary between air and water, which function as 2 transparent layers?
What methodology is based on curpic ions complexing with peptide bonds in an alkaline medium to produce a purple-colored complex?
What methodology is a technique that allows proteins to bind to a dye, forming a protein-dye complex that results in a shift of the maximum absorbance of the dye?
Dye binding techniques
What reagent is generally used in dye binding techniques?
Coomassie brilliant blue
What technique is used for the determination of total protein but is considered too cumbersom for use in routine testing - it is considered the reference method of choice to validate the biuret method?
What electrophoresis is a type of zone electrophoresis in which protein separation is based on the isoelectric point (pI)?
Name the Immunochemical methods
- Homogeneous and heterogeneous immunoassays
- Radial immunodiffusion (RID)
What is the test methodology for albumin?
Dye binding techniques using bromcresol green and broncresol purple dyes allow albumin to be positively charged for binding to the anionic dye, forming an albumin-dye complex that results in a shift of the maximum absorbance of the dye
What is the test methodology for globulins?
- Globulins = Total Protein - Albumin
What is the calculation for globulins?
Globulins = Total Protein - Albumin
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