Test Catalog

Test Id : EGFRW

EGFR Targeted Mutation Analysis with ALK Reflex, Tumor

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying non-small cell lung cancers that may benefit from treatment with epidermal growth factor receptor -targeted therapies or anaplastic lymphoma kinase inhibitors

Reflex Tests
Lists tests that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial tests.

Test Id Reporting Name Available Separately Always Performed
LCAF ALK (2p23), Lung Cancer, FISH, Ts Yes No

Additional Tests
Lists tests that are always performed, at an additional charge, with the initial tests.

Test Id Reporting Name Available Separately Always Performed
SLIRV Slide Review in MG No, (Bill Only) Yes

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, the EGFR Gene, Mutation Analysis, 51 Mutation Panel, Tumor will always be performed. All specimens without an EGFR mutation will be automatically reflexed to testing for the ALK (2p23) rearrangement. Specimens with an identified EGFR mutation will result in cancellation of the LCAF test.

 

When this test is ordered, slide review will always be performed at an additional charge.

Method Name
A short description of the method used to perform the test

Polymerase Chain Reaction (PCR)

NY State Available
Indicates the status of NY State approval and if the test is orderable for NY State clients.

Yes

Reporting Name
Lists a shorter or abbreviated version of the Published Name for a test

EGFR with ALK Reflex, Tumor

Aliases
Lists additional common names for a test, as an aid in searching

2p23

ALK

ALK Fish

ALK-EML4

EGFR

EGFR-TKI

EGFR-tyrosine kinase inhibitor

EGFRX

Epidermal growth factor receptor

Erlotinib

Gefitinib

Lung carcinoma

Non small cell lung cancer

Non-small cell lung cancer

NSCLC

T790M

Amivantamab-vmjw

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, the EGFR Gene, Mutation Analysis, 51 Mutation Panel, Tumor will always be performed. All specimens without an EGFR mutation will be automatically reflexed to testing for the ALK (2p23) rearrangement. Specimens with an identified EGFR mutation will result in cancellation of the LCAF test.

 

When this test is ordered, slide review will always be performed at an additional charge.

Specimen Type
Describes the specimen type validated for testing

Varies

Specimen Required
Defines the optimal specimen required to perform the test and the preferred volume to complete testing

Pathology report must accompany specimen in order for testing to be performed.

 

Preferred:

Specimen Type: Tissue

Container/Tube: Tissue block

Collection Instructions: Submit a formalin-fixed, paraffin-embedded tissue block.

 

Acceptable:

Specimen Type: Tissue

Container/Tube: Slides

Specimen Volume: 12 unstained, positively charged, unbaked slides or 2 hematoxylin and eosin-stained slides (will not be returned) and 10 unstained, positively charged, unbaked slides

Collection Instructions: Submit 12 unstained, positively charged, unbaked slides cut at 5-microns or 2 hematoxylin and eosin-stained slides and 10 unstained, positively charged, unbaked slides with 5-micron thick sections of the tumor tissue.

Forms

Specimen Minimum Volume
Defines the amount of sample necessary to provide a clinically relevant result as determined by the Testing Laboratory

See Specimen Required

Reject Due To
Identifies specimen types and conditions that may cause the specimen to be rejected

Specimens that have been decalcified (all methods)
Low tumor percentage
Insufficient amount of tumor
Specimens that have not been formalin-fixed, paraffin-embedded
Reject

Specimen Stability Information
Provides a description of the temperatures required to transport a specimen to the performing laboratory, alternate acceptable temperatures are also included

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
Refrigerated

Useful For
Suggests clinical disorders or settings where the test may be helpful

Identifying non-small cell lung cancers that may benefit from treatment with epidermal growth factor receptor -targeted therapies or anaplastic lymphoma kinase inhibitors

Testing Algorithm
Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

When this test is ordered, the EGFR Gene, Mutation Analysis, 51 Mutation Panel, Tumor will always be performed. All specimens without an EGFR mutation will be automatically reflexed to testing for the ALK (2p23) rearrangement. Specimens with an identified EGFR mutation will result in cancellation of the LCAF test.

 

When this test is ordered, slide review will always be performed at an additional charge.

Clinical Information
Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Targeted cancer therapies are defined as antibody or small molecule drugs that block the growth and spread of cancer by interfering with specific cell molecules involved in tumor growth and progression. Multiple targeted therapies have been approved by the FDA for treatment of specific cancers. Molecular genetic profiling is often needed to identify targets amenable to targeted therapies and to minimize treatment costs and therapy-associated risks. Epidermal growth factor receptor (EGFR) protein is activated by the binding of specific ligands, resulting in activation of the RAS/MAPK pathway. Activation of this pathway induces a signaling cascade, ultimately leading to cell proliferation. Dysregulation of the RAS/MAPK pathway is a key factor in tumor progression for many solid tumors. Targeted therapies directed to tumors harboring activating mutations within the EGFR tyrosine kinase domain (exons 18-21) have demonstrated some success in treating a subset of patients with non-small cell lung cancer (NSCLC). As a result, the mutation status of EGFR can be a useful marker by which patients are selected for EGFR-targeted therapy.

 

Rearrangements of the anaplastic lymphoma kinase (ALK) locus are found in a subset of lung carcinomas (generally EGFR wildtype tumors) and their identification by fluorescence in situ hybridization (FISH) may guide important therapeutic decisions for the management of these tumors. The fusion of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the ALK gene results from an inversion of chromosome band 2p23. The ALK-EML4 rearrangement has been identified in 3% to 5% of NSCLC with the majority occurring in adenocarcinoma and younger male patients who were light or nonsmokers. Recent studies have demonstrated that lung cancers harboring ALK rearrangements are resistant to EGFR tyrosine kinase inhibitors but may be highly sensitive to ALK inhibitors, like crizotinib (Xalkori). The drug crizotinib works by blocking certain kinases, including those produced by the abnormal ALK gene. Clinical studies have demonstrated that crizotinib treatment of patients with tumors exhibiting ALK rearrangements can halt tumor progression or result in tumor regression. The ALK/EML4 FISH assay is an FDA-approved companion diagnostic test for crizotinib, which was recently approved by the FDA to treat certain patients with late-stage (locally advanced or metastatic), non-small cell lung cancers that harbor ALK gene rearrangements. It is useful for the identification of patients with lung cancer who will benefit from crizotinib therapy.

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

An interpretive report will be provided.

Cautions
Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

A negative (wildtype) EGFR result does not rule out the presence of a mutation that may be present but is below the limits of detection for this assay (approximately 10%).

 

A negative (wildtype) EGFR result does not rule out the presence of other activating mutations in the EGFR

gene.

 

Rare polymorphisms exist that could lead to false-negative or false-positive EGFR results.

 

The ALK fluorescence in situ hybridization (FISH) test is intended to be used for therapeutic purposes in pulmonary carcinoma. This FISH assay does not rule out other chromosome abnormalities.

 

While results of these tests may indicate the likely response to EGFR-targeted therapies or  anaplastic lymphoma kinase (ALK)-inhibitor therapies, selection of treatment remains a clinical decision.

Clinical Reference
Recommendations for in-depth reading of a clinical nature

1. Sharma SV, Bell DW, Settleman J, Haber DA: Epidermal growth factor receptor mutations in lung cancer. Nat Rev Cancer. 2007 Mar;7(3):169-181. doi: 10.1038/nrc2088

2. Gao G, Ren S, Li A, et al: Epidermal growth factor receptor-tyrosine kinase inhibitor therapy is effective as first- line treatment of advanced non-small-cell lung cancer with mutated EGFR: a meta-analysis from six phase III randomized controlled trials. Int J Cancer. 2012 Sep 1;131(5):E822-829. doi: 10.1002/ijc.27396

3. Mok TS: Personalized medicine in lung cancer: what we need to know. Nat Rev Clin Oncol. 2011 Aug 23;8(11):661-668. doi: 10.1038/nrclinonc.2011.126

4. Cheng L, Alexander RE, Maclennan GT, et al: Molecular pathology of lung cancer: key to personalized medicine. Mod Path 2012 Mar;25(3):346-369. doi: 10.1038/modpathol.2011.215

Method Description
Describes how the test is performed and provides a method-specific reference

All ordered specimens will undergo EGFR testing. The EGFR test is a qualitative polymerase chain reaction (PCR)-based assay employing fluorescently labeled probes that are used to detect exon 18 (G719A/C/S), exon 21 (L858R,

L861Q), exon 20 (T790M, S768I) mutations, exon 19 deletions and exon 20 insertions of the EGFR gene.

 

Exon

Mutation

Protein change

Nucleotide change

Genotyp

18

G719A

p.Gly719Ala

c.2156G>C

G719A/C/S

G719C

p.Gly719Cys

c.2155G>T

G719C

p.Gly719Cys(2)

c.2154_2155delinsTT

G719S

p.Gly719Ser

c.2155G>A

19

Deletion 9

p.Leu747_Ala750delinsPro

c.2238_2248delinsGC

Exon 19 deletion

c.2239_2248delinsC

p.Leu747_Ala750delinsSer

c.2240_2248del

p.Leu747_Glu749del

c.2239_2247del

Deletion 12

p.Leu747_Thr751delinsPro

c.2239_2251delinsC

p.Leu747_Thr751delinsSer

c.2240_2251del

Deletion 15

p.Glu746_Ala750del

c.2235_2249del

c.2236_2250del

p.Leu747_Thr751del

c.2239_2253del

c.2240_2254del

c.2238_2252del

p.Glu746_Thr751delinsAla

c.2237_2251del

p.Glu746_Thr751delinsIle

c.2235_2252delinsAAT

p.Glu746_Thr751delinsVal

c.2237_2252delinsT

p.Lys745_Ala750delinsThr

c.2234_2248del

p.Glu746_Thr751delinsLeu

c.2236_2253delinsCTA

p.Glu746_Thr751delinsVal

c.2237_2253delinsTA

p.Glu746_Thr751delinsAla

c.2235_2251delinsAG

p.Glu746_Thr751delinsGln

c.2236_2253delinsCAA

p.Ile744_Ala750delinsValLys

c.2230_2249delinsGTCAA

Deletion 18

p.Leu747_Pro753delinsSer

c.2240_2257del

p.Glu746_Ser752delinsVal

c.2237_2255delinsT

p.Leu747_Ser752del

c.2239_2256del

p.Glu746_Thr751del

c.2236_2253del

p.Leu747_Pro753delinsGln

c.2239_2258delinsCA

p.Glu746_Ser752delinsAla

c.2237_2254del

p.Glu746_Ser752delinsAsp

c.2238_2255del

p.Glu746_Pro753delinsValSer

c.2237_2257delinsTCT

p.Glu746_Ser752delinsIle

c.2236_2255delinsAT

c.2236_2256delinsATC

p.Glu746_Ser752delinsVal

c.2237_2256delinsTT

c.2237_2256delinsTC

c.2235_2255delinsGGT

p.Leu747_Pro753del

c.2238_2258del

p.Glu746_Ser752del

c.2236_2256del

p.Ser752_Ile759del

c.2253_2276del

p.Thr790Met

c.2369C>T

p.Ser768Ile

c.2303G>T

p.Asp770_Asn771insGly

c.2310_2311insGGT

p.Val769_Asp770insAlaSerVal

c.2307_2308insGCCAGCGTG

p.Val769_Asp770insAlaSerVal

c.2309_2310delinsCCAGCGTGGAT

p.Asp770_Asn771insSerValAsp

c.2311_2312insGCGTGGACA

p.His773_Val774insHis

c.2319_2320insCAC

p.Leu858Arg

c.2573T>G

c.2573_2574delinsGT

c.2573_2574delinsGA

p.Leu861Gln

c.2582T>A

 

 

A pathology review and macrodissection to enrich for tumor cells is performed prior to slide scraping.

 

The ALK fluorescence in situ hybridization (FISH) test uses an FDA-approved ALK dual-color, break-apart rearrangement probe kitset. The ALK probe consists of 2 probes that flank the ALK gene region at 2p23 (Abbott Molecular). Five-micron sections of formalin-fixed, paraffin-embedded tissue specimens are cut and mounted on positively-charged glass slides. The selection of tissue and the identification of target areas on the hematoxylin and eosin-stained slide are performed by a pathologist. The probe set is hybridized to the appropriate target areas and 2 technologists analyze 25 interphase nuclei each (50 total). Results are reported based on the guidelines include with the probe kit and package insert with the results expressed as the percent abnormal nuclei.(Unpublished Mayo method)

PDF Report
Indicates whether the report includes an additional document with charts, images or other enriched information

No

Day(s) Performed
Outlines the days the test is performed. This field reflects the day that the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time before the test is performed. Some tests are listed as continuously performed, which means that assays are performed multiple times during the day.

Monday through Friday

Report Available
The interval of time (receipt of sample at Mayo Clinic Laboratories to results available) taking into account standard setup days and weekends. The first day is the time that it typically takes for a result to be available. The last day is the time it might take, accounting for any necessary repeated testing.

5 to 14 days

Specimen Retention Time
Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded

Unused portions of blocks will be returned. Unused slides are stored indefinitely.

Performing Laboratory Location
Indicates the location of the laboratory that performs the test

Rochester

Fees
Several factors determine the fee charged to perform a test. Contact your U.S. or International Regional Manager for information about establishing a fee schedule or to learn more about resources to optimize test selection.

  • Authorized users can sign in to Test Prices for detailed fee information.
  • Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
  • Prospective clients should contact their Regional Manager. For assistance, contact Customer Service.

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 instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR) product.

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

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 Clinic Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.

CPT codes are provided by the performing laboratory.

81235-EGFR (epidermal growth factor receptor) (eg, non-small cell lung cancer) gene analysis, common variants(eg, exon 19 deletions, L858R, T790M, G719S, L861Q)

88381-Microdissection, manual

88271 x 2-DNA Probe (if appropriate)

88274-Interphase in situ hybridization (if appropriate)

88291-Interpretation and report (if appropriate)

LOINC® Information
Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the order and results codes of this test. LOINC values are provided by the performing laboratory.

Test Id Test Order Name Order LOINC Value
EGFRW EGFR with ALK Reflex, Tumor 21665-5
Result Id Test Result Name Result LOINC Value
Applies only to results expressed in units of measure originally reported by the performing laboratory. These values do not apply to results that are converted to other units of measure.
616130 Result Summary 50397-9
616131 Result 21665-5
616132 Interpretation 69047-9
616133 Specimen 31208-2
616134 Source 31208-2
616135 Tissue ID 80398-1
616136 Released By 18771-6

Test Setup Resources

Setup Files
Test setup information contains test file definition details to support order and result interfacing between Mayo Clinic Laboratories and your Laboratory Information System.

Excel | Create a PDF

Sample Reports
Normal and Abnormal sample reports are provided as references for report appearance.

Normal Reports | Abnormal Reports

SI Sample Reports
International System (SI) of Unit reports are provided for a limited number of tests. These reports are intended for international account use and are only available through MayoLINK accounts that have been defined to receive them.

SI Normal Reports | SI Abnormal Reports