Christina Selinger1, Wendy Cooper1,2,3, Trina Lum1, Catriona McNeil4, Adrienne Morey5, Paul Waring6, Benhur Amanuel7,8, Michael Millward9,10, Joanne Peverall7, Chris Van Vliet7,8, Michael Christie6,11, Yen Tran12, Connie Diakos13, Nick Pavlakis13, Anthony J Gill3,13,14, Sandra O'Toole1,15. 1. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 2. School of Medicine, University of Western Sydney, Campbelltown, NSW, Australia. 3. Sydney Medical School, University of Sydney, Sydney, NSW, Australia. 4. Chris O'Brien Lifehouse and Royal Prince Alfred Hospital, Camperdown, NSW, Australia. 5. SydPath, Anatomical Pathology, St Vincent's Hospital, Darlinghurst, NSW, Australia. 6. Department of Pathology, University of Melbourne, Melbourne, Vic., Australia. 7. PathWest, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 8. School of Pathology and Laboratory Medicine, University of Western Australia, Nedlands, WA, Australia. 9. School of Medicine and Pharmacology, University of Western Australia, Nedlands, WA, Australia. 10. Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia. 11. Department of Anatomical Pathology and Medical Oncology, The Royal Melbourne Hospital, Parkville, Vic., Australia. 12. Ballarat Base Hospital, Ballarat, Vic., Australia. 13. Royal North Shore Hospital, St Leonards, NSW, Australia. 14. Cancer Diagnosis and Pathology Research Group, Kolling Institute of Medical Research, St Leonards, NSW, Australia. 15. The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Abstract
AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib. The aim of this study was to evaluate the ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with equivocal ALK status. METHODS AND RESULTS: ALK FISH was prospectively performed on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK break-apart probe (Abbott Molecular). ALK immunohistochemistry was performed with 5A4 and D5F3 antibodies. Fourteen cases had equivocal ALK status, based on borderline or focal FISH positivity, an atypical FISH pattern, or discrepancy between ALK FISH and immunohistochemistry. Four of the 14 equivocal cases showed discordance between the two FISH probes. All other cases were concordant. The TriCheck probe showed that, of 31 unequivocal cases, 15 were ALK-rearranged, and 60% of these had EML4 as the translocation partner. Within the group of 14 equivocal cases, 12 showed rearrangement with the Tricheck probe; only one of these showed EML4 rearrangement. Of the six equivocal cases that received crizotinib, four showed clinical benefit. CONCLUSIONS: The ALK/EML4 TriCheck FISH probe may be useful for the detection of ALK rearrangements, especially in borderline or atypical cases, where an additional unique ALK FISH probe may provide further confirmation of rearrangement.
AIMS: Accurate assessment of anaplastic lymphoma kinase (ALK) gene rearrangement in non-small-cell lung cancers (NSCLCs) is critical to identify patients who are likely to respond to crizotinib. The aim of this study was to evaluate the ALK/EML4 TriCheck FISH probe in a series of NSCLCs enriched for tumours with equivocal ALK status. METHODS AND RESULTS:ALK FISH was prospectively performed on 45 NSCLCs with the ALK/EML4 TriCheck probe (ZytoVision) and the Vysis ALK break-apart probe (Abbott Molecular). ALK immunohistochemistry was performed with 5A4 and D5F3 antibodies. Fourteen cases had equivocal ALK status, based on borderline or focal FISH positivity, an atypical FISH pattern, or discrepancy between ALK FISH and immunohistochemistry. Four of the 14 equivocal cases showed discordance between the two FISH probes. All other cases were concordant. The TriCheck probe showed that, of 31 unequivocal cases, 15 were ALK-rearranged, and 60% of these had EML4 as the translocation partner. Within the group of 14 equivocal cases, 12 showed rearrangement with the Tricheck probe; only one of these showed EML4 rearrangement. Of the six equivocal cases that received crizotinib, four showed clinical benefit. CONCLUSIONS: The ALK/EML4 TriCheck FISH probe may be useful for the detection of ALK rearrangements, especially in borderline or atypical cases, where an additional unique ALK FISH probe may provide further confirmation of rearrangement.
Authors: Tamkin Ahmadzada; Steven Kao; Glen Reid; Michael Boyer; Annabelle Mahar; Wendy A Cooper Journal: J Clin Med Date: 2018-06-15 Impact factor: 4.241