Test ID: ZAP70
ZAP-70, Chronic Lymphocytic Leukemia (CLL) Prognosis
NY State Approved 
Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
A risk factor for disease progression in patients with B-cell chronic lymphocytic leukemia
Additional Tests Lists test(s) that are always performed, at an additional charge, with the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| 88465 | Flow Cytometry Interp, 2-8 Markers | No, (Bill Only) | Yes |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
When this test is ordered, flow cytometry interpretation, 2 to 8 markers will always be performed at an additional charge.
Method Name A short description of the method used to perform the test
Flow Cytometry
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
CLL (Chronic Lymphocytic Leukemia)
ZAP 70
Zeta Associated Protein
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Specimen must arrive within 72 hours of draw.
Container/Tube: Yellow top (ACD solution B)
Specimen Volume: 6 mL
Collection Instructions: Specimen must be refrigerated within 9 hours of draw.
Forms: If not ordering electronically, please submit a Hematopathology/Molecular Oncology Request Form (Supply T241) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | NA |
| Icterus | NA |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| Whole Blood ACD-B | Refrigerated | 72 hours |
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
B-cell chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. Its clinical course is highly variable with survival times ranging from months to decades. The standard procedure for estimating prognosis is clinical staging systems developed by Rai and Binet. In these staging systems, most CLL patients have early-stage disease. Genetic prognostic markers such as immunoglobulin heavy chain gene mutational status and FISH studies for specific chromosomal abnormalities have now been developed to refine the risk of progressive disease. CD38 and ZAP-70 have been identified as surrogate markers for mutation status and can be evaluated by flow cytometric immunophenotyping.
ZAP-70 (70-kDa zeta-associated protein) is an intracellular tyrosine kinase discovered initially because of its role in T-cell signaling. It has also been found to be associated with the B-cell receptor in CLL. The expression of ZAP-70 (>20% of B cells) has been associated with an increased risk for an adverse outcome in B-cell CLL and is considered an important risk factor in these patients. ZAP-70 expression, if present, is constant throughout the patient's clinical course and thus is a valid risk marker regardless of when it is evaluated.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
An interpretive report will be provided.
Interpretation Provides information to assist in interpretation of the test results
ZAP-70 expression is considered to be a risk factor for disease progression in patients with B cell chronic lymphocytic leukemia (CLL).
The threshold for ZAP70 staining is established by using normal B cells as the negative cutoff value and comparing with background positive T-cell staining.
-ZAP-70-negative (<20% of monoclonal B cells) CLL patients have a median time to treatment of 9.2 years.
-ZAP-70-positive (>20% of monoclonal B cells) CLL patients have a median time to treatment of 2.9 years.
See ZAP70 Expression and Overall Survival Among Patients with B-Cell CLL in Multimedia for survival curves.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
ZAP-70 is an intracellular activation marker in chronic lymphocytic leukemia (CLL) cells and expression can be labile after 24 hours. Failure to follow specimen processing, transportation, and storage requirements may lead to false results.
Bone marrow, lymph node, and tissue specimens will not be accepted as these specimen types have not been clinically validated at Mayo or in literature studies. Since B-cell CLL is, by definition, a peripheral leukemic process and since blood specimens can be easily obtained, this should not be a significant limitation.
A ZAP-70 study may be rejected if the histogram pattern indicates that there has been any cellular changes that could prevent accurate interpretation of antigen expression.
Prior documented flow cytometric diagnosis of CLL is required before testing for ZAP-70. Specimens submitted for LCMS/3287 Leukemia/Lymphoma Immunophenotyping by Flow Cytometry will not be optimal for ZAP-70 testing due to the time delay and differences in specimen handling requirements. It is suggested that a second blood specimen be submitted for ZAP-70.
If no immunoglobulin light chain-restricted B cells are identified, then no ZAP-70 results will be reported.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Rassenti LZ, Huynh L, Toy TL, et al: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 2004 August 26;351(9):893-901
2. Crespo M, Bosch F, Villamor N, et al: ZAP-70 expression as a surrogate for immunoglobulin-variable-region mutations in chronic lymphocytic leukemia. N Engl J Med 2003 May 1;348(18):1764-1765
3. Orchard JA, Ibbotson RE, Davis Z, et al: ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 2004 January 10;363(9403):105-111
Method Description Describes how the test is performed and provides a method-specific reference
Ficoll-separated cells are initially stained with CD3 and CD19, then treated with saponin and incubated with ZAP-70 antibody. Flow cytometry is used to determine the percent of B cells positive for ZAP-70. Staining is also performed on a normal peripheral blood control specimen. The threshold for ZAP-70 staining is established by using normal B cells as the negative cutoff value and comparing with background-positive T-cell staining.(Rassenti LZ, Huynh L, Toy TL, et al: ZAP-70 compared with immunoglobulin heavy-chain gene mutation status as a predictor of disease progression in chronic lymphocytic leukemia. N Engl J Med 2004 August 26;351[9]:893-901)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
Monday through Friday; 9 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
ZAP-70, Chronic Lymphocytic Leukemia (CLL) Prognosis
88184-Flow cytometry
88185 x 2-Additional markers
Flow Cytometry Interpretation, 2 to 8 Markers
88187
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 19518 | Accession Number | N/A |
| 19519 | Referring Pathologist/Physician | 46608-6 |
| 19520 | Ref. Path Address | In Process |
| 19521 | Material | In Process |
| 19522 | Specimen: | 31208-2 |
| 19523 | Bone Marrow Differential | 47286-0 |
| 19524 | Peripheral Blood: | N/A |
| 19525 | Aspirate: | N/A |
| 19526 | Biopsy | 52121-1 |
| 19527 | Microscopic Description | In Process |
| 19528 | Special Studies | N/A |
| 19529 | Final Diagnosis | 22637-3 |
| 19530 | Comment: | 48767-8 |
| 19531 | Revision Description: | In Process |
| 19532 | Signing Pathologist | 19139-5 |
| 19533 | Special Procedures | N/A |
| 19534 | SP Signing Pathologist | N/A |
| 19535 | *Previous Report Follows* | N/A |
| 19536 | Addendum | 35265-8 |
| 19537 | Addendum Comment: | 22638-1 |
| 19538 | Addendum Pathologist: | 19139-5 |
External
link
PDF
document
Excel
document
Word
document