Large-Scale Screening and Molecular Characterization of EML4-ALK Fusion Variants in Archival Non–Small-Cell Lung Cancer Tumor Specimens Using Quantitative Reverse Transcription Polymerase Chain Reaction Assays

Li, Tianhong; Maus, Martin K. H.; Desai, Sonal J.; Beckett, Laurel A.; Stephens, Craig; Huang, Eric C.; Hsiang, Jack; Zeger, Gary; Danenberg, Kathleen D.; Astrow, Stephanie H.; Gandara, David R.

doi:10.1097/jto.0000000000000030

Cited by 55 publications

(49 citation statements)

References 47 publications

(71 reference statements)

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“…19 26 There are two different RT-PCR approaches for ALK testing. One uses probes for both fusion genes (ALK and EML4/KIF5B/ HIP133), [27][28][29][30] while the other compares different levels of amplification of small PCR products (5 0 and 3 0 portions of ALK transcripts) on the ALK gene (fusion partner independent). 31 32 The first approach has a sensitivity of approximately 90% (depending on the coverage of fusion partners), while theoretically the latter approach has 100% sensitivity.…”

Section: Testing Procedures For Detection Of Egfr and Alk Status In Lmentioning

confidence: 99%

Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Dietel

Bubendorf

Dingemans

et al. 2015

Thorax

155

159

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BackgroundThere is currently no Europe-wide consensus on the appropriate preanalytical measures and workflow to optimise procedures for tissue-based molecular testing of non-small-cell lung cancer (NSCLC). To address this, a group of lung cancer experts (see list of authors) convened to discuss and propose standard operating procedures (SOPs) for NSCLC.MethodsBased on earlier meetings and scientific expertise on lung cancer, a multidisciplinary group meeting was aligned. The aim was to include all relevant aspects concerning NSCLC diagnosis. After careful consideration, the following topics were selected and each was reviewed by the experts: surgical resection and sampling; biopsy procedures for analysis; preanalytical and other variables affecting quality of tissue; tissue conservation; testing procedures for epidermal growth factor receptor, anaplastic lymphoma kinase and ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) in lung tissue and cytological specimens; as well as standardised reporting and quality control (QC). Finally, an optimal workflow was described.ResultsSuggested optimal procedures and workflows are discussed in detail. The broad consensus was that the complex workflow presented can only be executed effectively by an interdisciplinary approach using a well-trained team.ConclusionsTo optimise diagnosis and treatment of patients with NSCLC, it is essential to establish SOPs that are adaptable to the local situation. In addition, a continuous QC system and a local multidisciplinary tumour-type-oriented board are essential.

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Section: Testing Procedures For Detection Of Egfr and Alk Status In Lmentioning

confidence: 99%

Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Dietel

Bubendorf

Dingemans

et al. 2015

Thorax

155

159

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“…[8][9][10][11] However, so far there is no report on the validation of an easily obtainable commercial kit as an ALK mutation screening tool for practical purposes. We clinically validated the kit using total nucleic acid extracted from FFPE tissues.…”

Section: Commentmentioning

confidence: 99%

Clinical Validation of a Novel Commercial Reverse Transcription–Quantitative Polymerase Chain Reaction Screening Assay for Detection of ALK Translocations and Amplifications in Non–Small Cell Lung Carcinomas

Liu

Pepper

Hendrickson

et al. 2015

Archives of Pathology &Amp; Laboratory Medicine

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Context.-EGFR mutations and anaplastic lymphoma kinase (ALK) translocations have significant biologic and therapeutic implications in lung cancers, particularly lung adenocarcinomas. ALK translocations are less frequent compared with EGFR mutations; interestingly, these two abnormalities are most commonly mutually exclusive. The 2013 College of American Pathologists/Association for Molecular Pathology/International Association for the Study of Lung Cancer molecular testing guideline for lung cancers recommend a testing algorithm in which detection of ALK translocations using fluorescence in situ hybridization (FISH) is to be performed following testing for EGFR mutations. Such an algorithm is cost-effective but potentially slows down turnaround time; and as a secondary test, ALK FISH assay may not be completed because it requires the use of additional tissue, and the small biopsies or cytology specimens may have been exhausted in the extraction of nucleic acid for EGFR mutation screening.Objective.-To provide efficient testing of both EGFR and ALK genetic alterations in small biopsies and cytology specimens.Design.-We validated a highly sensitive ALK reverse transcription-quantitative polymerase chain reaction (RTqPCR) assay as a screening tool for ALK translocations and amplifications.Results.-We performed a retrospective review of cases previously tested by FISH and found that all FISH ALK translocation-positive specimens were RT-qPCR positive, and all FISH ALK translocation-negative cases were RTqPCR negative (the sensitivity and specificity of the ALK RT-qPCR assay were 100%).Conclusion.-This assay allows rapid identification of ALK alterations, can be performed in conjunction with EGFR testing, and does not require use of valuable additional tumor tissue.

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“…The level of thymidylate synthase in ALK-positive cells has been found to be significantly lower compared with control cells, and this could explain the higher sensitivity to pemetrexed of these tumors (24). Similarly, molecular analysis performed in a subset of a large cohort of North-American NSCLC patients showed that the median thymidilate synthase level in 85 ALK-positive cases was significantly lower than the level in ALK-negative lung adenocarcinomas (29).…”

Section: Role Of Chemotherapy In Alk-positive Casesmentioning

confidence: 94%

Diagnostic and therapeutic issues for patients with advanced non-small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (Review)

Maïo

Marinis

Hirsch

et al. 2014

International Journal of Oncology

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The recent availability of crizotinib in clinical practice, for the treatment of patients with advanced non-small cell lung cancer (NSCLC) selected by the presence of anaplastic lymphoma kinase (ALK) rearrangement, has relevant implications for both the diagnostic phase and the treatment choices. In the United States, crizotinib was approved by the Food and Drug Administration (FDA) in 2011 for patients with ALK positivity detected by FDA-approved companion diagnostic test. As of January, 2014, the only FDA-approved diagnostic test is Vysis ALK Break-Apart FISH Probe Kit. In Europe, European Medicines Agency (EMA) approved crizotinib for ALK-positive patients in 2012, without specifying the type of test used for determining the positivity. FISH remains the reference technique for ALK determination, but, if fully validated, immunohistochemistry could challenge the current ALK screening practice. Given the robust evidence of activity of crizotinib in ALK-positive patients both pretreated and chemotherapy-naïve, and the favourable tolerability profile of the drug, many oncologists would prefer to administer the drug as early as possible. This is technically feasible in the United States, where crizotinib was approved well before the availability of the results of the randomized phase III trial comparing the drug with standard second-line chemotherapy, and the use of crizotinib in ALK-positive patients is not restricted to a specific line of treatment. On the contrary, in Europe, differently from the FDA decision, crizotinib cannot be used in chemotherapy-naïve patients. In both realities, a deeper knowledge of mechanisms of resistance, the role of repeated biopsies, the treatment strategy for patients experiencing disease progression with crizotinib, the choice of the best chemotherapy regimen are challenging topics for the management of ALK-positive patients in clinical practice.

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Large-Scale Screening and Molecular Characterization of EML4-ALK Fusion Variants in Archival Non–Small-Cell Lung Cancer Tumor Specimens Using Quantitative Reverse Transcription Polymerase Chain Reaction Assays

Cited by 55 publications

References 47 publications

Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group

Clinical Validation of a Novel Commercial Reverse Transcription–Quantitative Polymerase Chain Reaction Screening Assay for Detection of ALK Translocations and Amplifications in Non–Small Cell Lung Carcinomas

Diagnostic and therapeutic issues for patients with advanced non-small cell lung cancer harboring anaplastic lymphoma kinase rearrangement: European vs. US perspective (Review)

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