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IASLC ATLAS OF ALK TESTING IN LUNG CANCER
Section III. How Should ALK Testing Be Performed?
Question 9. What Methods Should Be Used for ALK testing? 9.1: Recommendation: Laboratories should use an ALK FISH assay using dual-labeled break-apart probes for selecting patients for ALK TKI therapy; ALK immunohistochemistry, if carefully validated, may be considered as a screening methodology to select specimens for ALK FISH testing. 9.2: Recommendation: RT-PCR is not recommended as an alternative to FISH for selecting patients for ALK inhibitor therapy. 9.3: Expert consensus opinion: A pathologist should be involved in the selection of sections for ALK FISH testing, by assessing tumor architecture, cytology, and specimen quality. 9.4: Expert consensus opinion: A pathologist should participate in the interpretation of ALK FISH slides, either by performing the analysis directly or by reviewing the interpretations of cytogeneticists or technologists with specialized training in solid tumor FISH analysis. 9.5: Expert consensus opinion: Testing for secondary mutations in ALK associated with acquired resistance to ALK inhibitors is not currently required for clinical management.
Section IV. Should Other Genes Be Routinely Tested in Lung Adenocarcinoma?
Question 10. Are Other Molecular Markers Suitable for Testing in Lung Cancer? 10.1a: Recommendation: Testing for EGFR should be prioritized over other molecular markers in lung adenocarcinoma. 10.1b: Suggestion: After EGFR testing, testing for ALK should be prioritized over other proposed molecular markers in lung adenocarcinoma, for which published evidence is insufficient to support testing guideline development at the present time.
Section V. How Should Molecular Testing of Lung Adenocarcinomas Be Implemented and Operationalized?
Question 11. Must All Adenocarcinomas Be Tested for Both EGFR and ALK? 11.1: Expert consensus opinion: Laboratories may implement testing algorithms to enhance the efficiency of molecular testing of lung adenocarcinomas, provided the overall turnaround time requirements are met. Question 12. How Should EGFR and ALK Results Be Reported? 12.1: Expert consensus opinion: EGFR mutation testing reports and ALK FISH reports should include a results and interpretation section readily understandable by oncologists and by nonspecialist pathologists. Question 13. How Should EGFR and ALK Testing Be Validated? 13.1: Expert consensus opinion: EGFR and ALK testing validation should follow the same guidelines as for other molecular diagnostics and FISH tests. Question 14. How Should Quality Assurance Be Maintained? 13.1: Expert consensus opinion: Laboratories should follow similar quality control and quality assurance policies and procedures for EGFR and ALK testing in lung cancers as for other clinical laboratory assays. In particular, laboratories performing EGFR and ALK testing for TKI therapy should enroll in proficiency testing, if available.
Abbreviations: CISH, chromogenic in situ hybridization; EGFR, epidermal growth factor receptor; FISH, fluorescence in situ hybridization; PCR, polymerase chain reaction; RT-PCR, reverse transcription-polymerase chain reaction; TKI, tyrosine kinase inhibitor; TNM, tumor node metastasis. Lindeman NI, Cagle PT, Beasley MB, et al. Molecular testing guideline for selection of lung cancer patients for EGFR and ALK tyrosine kinase inhibitors: Guideline from the College of American Pathologists (CAP), International Association for the Study of Lung Cancer (IASLC), Association for Molecular Pathology (AMP). J Thorac Oncol 2013;8:823-859.