7 TUMOR TESTING AND TRANSPLANTATION Flashcards
(1) A patient had surgery for colorectal cancer, after which he received chemotherapy for 6 months. The test for carcinoembryonic antigen (CEA) was normal at this time. One year later, the bimonthly level of CEA was elevated (above 10 ng/mL). An examination and biopsy revealed recurrence of a small tumor. What was the value of the results provided by the
CEA test in this clinical situation?
A. Diagnostic information
B. Information for further treatment
C. Information on the immunologic response of the patient
D. No useful clinical information in this case
B. Information for further treatment
CEA is a glycoprotein that is elevated in about 60% of patients with colorectal cancer and one third or more patients with pulmonary, gastric, and pancreatic cancers. CEA may be positive in smokers and in patients with cirrhosis, Crohn disease, and other nonmalignant conditions. Because sensitivity for malignant disease is low, CEA is not recommended for use as a diagnostic test. However, an elevated CEA level after treatment is evidence of tumor recurrence and the need for second-look surgery.
A carbohydrate antigen 125 assay (CA-125) was performed on a woman with ovarian cancer. After treatment, the levels fell significantly. An examination performed later revealed recurrence of the tumor, but the CA-125 levels remained low. How can this finding be explained?
A. Test error
B. CA-125 was the wrong laboratory test; α fetoprotein (AFP) is a better test to monitor ovarian cancer
C. CA-125 may not be sensitive enough when used alone to monitor tumor development
D. CA-125 is not specific enough to detect only one type of tumor
C. CA-125 may not be sensitive enough when used alone to monitor tumor development
CA-125 is a tumor associated carbohydrate antigen that is elevated in 70% to 80% of patients with ovarian cancer and about 20% of patients with pancreatic cancer. Although an increase in CA-125 may indicate recurrent or progressive disease, low levels do not necessarily indicate the absence of tumor growth.
(3) What is the correct procedure upon receipt of a test request for human chorionic gonadotropin (hCG) on the serum of a 60-year-old man?
A. Return the request; hCG is not performed on men
B. Perform a qualitative hCG test to see if hCG is present
C. Perform the test; hCG may be increased in testicular tumors
D. Perform the test but use different standards and controls
C. Perform the test; hCG may be increased in testicular tumors
hCG is normally tested for in pregnancy; it is increased in approximately 60% of patients with testicular tumors and a lower percentage of those with ovarian, gastrointestinal, breast, and pulmonary tumors. Malignant cells secreting hCG may produce only the β-subunit; therefore, qualitative and quantitative tests that detect both intact hCG and free β-subunits provide better sensitivity than either test by itself.
(4) Would an hCG test using a monoclonal antibody against the β-subunit of hCG likely be affected by an increased level of follicle-stimulating hormone (FSH)?
A. Yes, the β-subunit of FSH is identical to that of hCG
B. No, the test would be specific for the β-subunit of hCG
C. Yes, a cross reaction would occur because of structural similarities
D. No, the structure of FSH and hCG are not at all similar
B. No, the test would be specific for the β-subunit of hCG
Luteinizing hormone, FSH, and hCG share a common α-subunit but have different β-subunits. A test for hCG using a monoclonal antibody would be specific for hCG, provided that the antibody was directed against an antigenic determinant on the carboxy terminal end of the β-subunit.
(5) Which of the following substances, sometimes used as a tumor marker, is increased two or threefold in a normal pregnancy?
A. Alkaline phosphatase (ALP)
B. Calcitonin
C. Adrenocortocotropic hormone (ACTH)
D. Neuron-specific enolase
A. Alkaline phosphatase (ALP)
Isoenzymes of ALP are sometimes used as tumor markers, but they have a low specificity because they are also increased in nonmalignant diseases. These include placental-like (heat-stable) ALP isoenzymes, which are found (infrequently) in some malignancies, such as cancer of the lung; bone derived ALP, which is a marker for metastatic bone cancer; and the fast-migrating liver isoenzyme, which is a marker for metastatic liver cancer. ACTH is secreted as an ectopic hormone in some patients with cancer of the lung. Calcitonin is a hormone produced by the medulla of the thyroid and is increased in the serum of patients with medullary thyroid carcinoma. Neuron-specific enolase is an enzyme that is used as a tumor marker primarily for neuroblastoma.
(6) What is an advantage of performing a prostate specific antigen (PSA) test for prostate cancer?
A. PSA is stable in serum and not affected by digital rectal examination
B. PSA is increased only in prostatic malignancy
C. A normal serum level rules out malignant prostatic disease
D. The percentage of free PSA is elevated in persons with malignant disease
A. PSA is stable in serum and not affected by digital rectal examination
PSA is a glycoprotein with protease activity that is specific for the prostate gland. High levels may be caused by prostate malignancy, benign prostatic hypertrophy, or prostatitis, but PSA is not increased by physical examination of the prostate. PSA has a sensitivity of 80% and a specificity of about 75% for prostate cancer. The sensitivity is sufficiently high to warrant its use in screening tests, but its sensitivity for stage A cancer is below 60%. Most of the serum PSA is bound to protease inhibitors, such as α1 antitrypsin and α1-antichymotrypsin. Patients with borderline PSA levels (4–10 ng/mL) and a low percentage of free PSA are more likely to have cancer of the prostate compared with patients with a normal percentage of free PSA.
(7) Which method is the most sensitive for quantitation of AFP?
A. Double immunodiffusion
B. Electrophoresis
C. Enzyme immunoassay
D. Particle agglutination
C. Enzyme immunoassay
AFP is a glycoprotein that is produced in about 80% to 90% of patients with hepatoma and in a lower percentage of patients with other tumors, including retinoblastoma, breast cancer, uterine cancer, and pancreatic cancer. The upper reference limit for serum is only 10 ng/mL, which requires a sensitive method of assay, such as EIA. The high analytical sensitivity of chemiluminescent immunoassays permits detection of reduced AFP levels in maternal serum associated with Down syndrome, as well as elevated levels associated with spina bifida.
(8) How is HLA typing used in the investigation of genetic diseases?
A. For prediction of the severity of the disease
B. For genetic linkage studies
C. For direct diagnosis of disease
D. Is not useful in this situation
B. For genetic linkage studies
HLA typing is useful in predicting some genetic diseases and for genetic counseling because certain HLA types show strong linkage to some diseases. HLA typing is not specifically used to diagnose a disease or assess its severity. In linkage studies, a disease gene can be predicted because it is located next to the locus of a normal gene with which it segregates. For example, the relative risk of developing ankylosing spondylitis is 87% in persons who are positive for HLA-B27. Analysis of family pedigrees for the linkage marker and disease can be used to determine the probability that a family member will inherit the disease gene.
(9) Select the best donor for a man, blood type AB, in need of kidney transplantation.
A. His brother, type AB, HLA matched for class II antigens
B. His mother, type B, HLA matched for class I antigens
C. His cousin, type O, HLA matched for major class II antigens
D. Deceased donor, type O, HLA matched for some class I and II antigens
A. His brother, type AB, HLA matched for class II antigens
A twin or sibling donor of the same blood type and HLA matched for class II antigens is the best donor in this situation. Class II antigens (HLA-D, -DR, -DQ, and -DP) determine the ability of the transplant recipient to recognize the graft. The HLA genes are located close together on chromosome 6, and crossover between HLA genes is rare. Siblings with closely matched class II antigens most likely inherited the same class I genes. The probability of siblings inheriting the same HLA haplotypes from both parents is 1:4.
(10) Interpret the following microcytotoxicity target cell results:
A9 and B12 cells = damaged; A1 and Aw19 cells = intact
A. Positive for A1 and Aw19; negative for A9 and B12
B. Negative for A1 and Aw19; positive for A9 and B12
C. Error in test system; retest
D. Impossible to determine
B. Negative for A1 and Aw19; positive for A9 and B12
The microcytotoxicity test is based on the reaction of specific antisera and HLA antigens on test cells. Cells damaged by the binding of antibody and complement are detected with a supravital dye, such as eosin.
(11) Which method, classically used for HLA-D typing, is often used to determine the compatibility between a living organ donor and a recipient?
A. Flow cytometry
B. Mixed lymphocyte culture (MLC)
C. Primed lymphocyte test
D. Restriction fragment length polymorphism (RFLP)
B. Mixed lymphocyte culture (MLC)
Flow cytometry can be used in transplantation to type serologically defined HLA antigens. The one way mixed lymphocyte reaction is used to identify HLA-D antigens on the donor’s lymphocytes and is used for crossmatching living donors with transplant recipients. The assay is time consuming and would not be used as part of a workup for a transplant from a deceased donor. HLA-D incompatibility is associated with the recognition phase of allograft rejection. The primed lymphocyte test is used to identify HLA-DP antigens.
(12) SITUATION: Cells type negative for all HLA antigens in a complement-dependent cytotoxicity assay. What is the most likely cause?
A. Too much supravital dye was added
B. Rabbit complement is inactivated
C. All leukocytes are dead
D. Antisera is too concentrated
B. Rabbit complement is inactivated
Inactive rabbit complement may not become fixed to antibodies that have bound test leukocytes; therefore, no lysis of cells will occur. When the supravital dye is added, all cells will appear negative (exclude the dye) for all HLAs.
(13) What method may be used for tissue typing instead of serological HLA typing?
A. PCR
B. Southern blotting
C. RFLP
D. All of these options
D. All of these options
PCR, Southern blotting, and testing for RFLPs may all be used to identify HLA genes. Many laboratories use PCR technology for the routine determination of HLA type.
