Test Catalog

Test Id : EGFRR

Lung Cancer, EGFR 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-tyrosine kinase 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, EGFR and LCAF testing will always be ordered. The EGFR Gene, Mutation Analysis, 29 Mutation Panel, Tumor, will always be performed. All specimens without an EGFR mutation will be automatically reflexed to LCAF / ALK (2p23), Lung Cancer, FISH Tissue. 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) and Fluorescence In Situ Hybridization (FISH)

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

Lung Cancer, EGFR with ALK Reflex

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

Epidermal growth factor receptor

Erlotinib

Gefitinib

Lung carcinoma

Non small cell lung cancer

Non-small cell lung cancer

NSCLC

EGFRX

T790M

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

When this test is ordered, EGFR and LCAF testing will always be ordered. The EGFR Gene, Mutation Analysis, 29 Mutation Panel, Tumor, will always be performed. All specimens without an EGFR mutation will be automatically reflexed to LCAF / ALK (2p23), Lung Cancer, FISH Tissue. 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

Formalin-fixed, paraffin-embedded tissue block (preferred) or 2 slides stained with hematoxylin-and-eosin and 10 unstained, positively charged, unbaked slides with 5-micron thick sections of the tumor tissue.

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

Tissue Specimens that have been decalcified (all methods); specimens that have not been formalin-fixed, paraffin-embedded

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)
Frozen
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-tyrosine kinase 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, EGFR and LCAF testing will always be ordered. The EGFR Gene, Mutation Analysis, 29 Mutation Panel, Tumor, will always be performed. All specimens without an EGFR mutation will be automatically reflexed to LCAF / ALK (2p23), Lung Cancer, FISH Tissue. 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

Lung cancer is the leading cause of cancer death in the United States. Non-small cell lung carcinoma (NSCLC) accounts for 75% to 80% of all lung cancers with an overall 5-year survival rate of 10% to 15%. Standard chemotherapy regimens have had marginal success in improving clinical outcomes. Epidermal growth factor receptor (EGFR) is activated by the binding of specific ligands, resulting in activation of the RAS/MAPK pathway. EGFR-targeted therapies (eg, gefitinib and erlotinib) have been approved by the FDA for use in treating patients with NSCLC who previously failed to respond to traditional chemotherapy. EGFR tyrosine kinase inhibitors have also been shown to increase progression-free and overall survival in patients who receive these therapies as a first-line therapy for the treatment of NSCLC. Agents such as gefitinib and erlotinib, which prevent ATP binding to EGFR kinase, do not appear to have any meaningful inhibitor activity on tumors that lack an activating EGFR mutation or in tumors that demonstrate the presence of drug-resistant EGFR mutations (eg, exon 20 insertions and T790M). Therefore, current data suggest that the efficacy of EGFR-targeted therapies in NSCLC is confined to patients with tumors demonstrating the presence of EGFR-activating mutations such as L858R, L861Q, G719A/S/C, S768I, or small deletions within exon 19 and the absence of drug-resistant mutations. As a result, the mutation status of EGFR is a critical marker for selecting patients for EGFR-targeted therapy.

 

Rearrangements of the anaplastic lymphoma kinase (ALK) locus are found in a subset of lung carcinomas (generally EGFR wild-type tumors) and their identification by FISH may guide important therapeutic decisions for the management of these tumors. The fusion of the EML4 (echinoderm microtubule-associated protein-like 4) gene with the ALK (anaplastic large cell lymphoma kinase) 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 epidermal growth factor receptor 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 lung cancer patients 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 (wild-type) EGFR result does not rule out the presence of a mutation that may be present, but below the limits of detection for this assay (approximately 5%).

 

A negative (wild-type) 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 FISH test (LCAF) 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 epidermal growth factor receptor (EGFR)-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;7(3):169-181

2. Gao G, Ren S, Li A, et al: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is effective as first-line treatment of advanced non-small-cell lung cancer with mutated EGFR: a meta-analysis from 6 phase III randomized controlled trials. Int J Cancer 2012 Sep 1;131(5):E822-829

3. Mok TS: Personalized medicine in lung cancer: What we need to know. Nat Rev Clin Oncol 2011;8:661-668

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

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 PCR-based assay employing Scorpions real-time PCR and allele-specific PCR technologies that is used to test for 29 mutations within exons 18 through 21 of the EGFR gene:

 

G719A

2239_2256del8

G719S

2239_2248TTAAGAGAAG->C

G719C

2239_2258->CA

2235_2249del15

2240_2251del12

2235_2252->AAT

2240_2257del8

2236_2253del18

2240_2254del15

2237_2251del15

2239_2251->C

2237_2254del18

2307_2308ins9

2237_2255->T

2310_2311insGGT

2236_2250del15,

2319_2320insCAC

2238_2255del18,

S768I

2238_2248->GC

T790M

2238_2252->GCA

L858R

2239_2247del9

L861Q

2239_2253del15

 

 

A pathology review and macrodissection to enrich for tumor cells is performed prior to DNA extraction.

 

In patients with no detectable EGFR mutations, ALK FISH testing will be performed. The ALK FISH test (LCAF) 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 has been modified from the manufacturer's instructions. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. 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.

EGFR Gene, Mutation Analysis, Tumor

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

 

Additional Tests:

Slide Review

88381-Microdissection, manual

 

Reflexed Tests (if appropriate):

Lung Cancer, ALK (2p23), FISH, Ts

88271 x 2-DNA Probe (if appropriate)

88274-Interphase in situ hybridization (if appropriate)

88291-Interpretation and report (if appropriate)

LOINC® Information

Test Id Test Order Name Order LOINC Value
EGFRR Lung Cancer, EGFR with ALK Reflex 21665-5
Result Id Test Result Name Result LOINC Value
Result LOINC Value Tooltip
53240 Result Summary 50397-9
53241 Result 21666-3
53242 Interpretation 69047-9
53243 Specimen 31208-2
53244 Source 31208-2
54441 Tissue ID 80398-1
53245 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 | 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