PMID- 31390053 OWN - NLM STAT- MEDLINE DCOM- 20200526 LR - 20200526 IS - 1097-0142 (Electronic) IS - 0008-543X (Linking) VI - 125 IP - 22 DP - 2019 Nov 15 TI - Anaplastic lymphoma kinase 5A4 immunohistochemistry as a diagnostic assay in lung cancer: A Canadian reference testing center's results in population-based reflex testing. PG - 4043-4051 LID - 10.1002/cncr.32422 [doi] AB - BACKGROUND: The presence of anaplastic lymphoma kinase (ALK) rearrangement predicts response to ALK tyrosine kinase inhibitor (TKI) therapy. Fluorescence in situ hybridization (FISH) was the initial reference standard to detect ALK rearrangement, but immunohistochemistry (IHC) using D5F3 has gained acceptance as an alternative diagnostic method. ALK IHC assays using other ALK antibodies have also been used as screening methods, but data supporting their utility as diagnostic tests have not been widely reported. METHODS: Data from reflexive clinical ALK IHC test using the 5A4 clone concurrent with epidermal growth factor receptor (EGFR) mutation testing were analyzed. ALK IHC results were reported as negative (-), equivocal, or positive (+), with equivocal or positive staining validated by FISH break-apart probe testing. Treatment outcomes were reviewed for ALK IHC+ patients. RESULTS: Between 2012 and 2015, 146 (2.5%) cases were reported as ALK IHC+, 188 (3.2%) were reported as equivocal, and 5624 (94.4%) were reported as ALK IHC-. Of the ALK IHC+ cases, 131/143(91.6%) were ALK FISH+. Excluding 6 cases in which FISH was inconclusive or not performed, the positive predictive value was 95.6%, and the negative predictive value was 100%. Most specimens (n = 5352 [89.6%]) were also successfully tested for EGFR. Clinical responses to ALK TKIs were noted in 49 ALK IHC+ patients, with a median progression-free survival of 9.9 months. CONCLUSIONS: ALK 5A4 IHC can serve as a robust diagnostic test for ALK-rearranged lung cancer and is associated with treatment response and survival. Optimized tissue allocation resulted in high success rates of combined reflex EGFR and ALK testing. CI - (c) 2019 American Cancer Society. FAU - Fiset, Pierre O AU - Fiset PO AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. AD - Department of Pathology, McGill University, Montreal, Quebec, Canada. FAU - Labbe, Catherine AU - Labbe C AD - Division of Hematology and Oncology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. AD - Institut Universitaire de Cardiologie et de Pneumologie de Quebec, Universite Laval, Quebec City, Quebec, Canada. FAU - Young, Kelvin AU - Young K AD - Division of Hematology and Oncology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Craddock, Kenneth J AU - Craddock KJ AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. AD - Department of Pathology, Southlake Regional Health Centre, Newmarket, Ontario, Canada. FAU - Smith, Adam C AU - Smith AC AUID- ORCID: 0000-0001-9927-4914 AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Tanguay, Jeffrey AU - Tanguay J AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Pintilie, Melania AU - Pintilie M AD - Department of Biostatistics, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. FAU - Wang, Ri AU - Wang R AD - Department of Biostatistics, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Centre for Urban Health Solutions, Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, Ontario, Canada. FAU - Torlakovic, Emina AU - Torlakovic E AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Cheung, Carol AU - Cheung C AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - da Cunha Santos, Gilda AU - da Cunha Santos G AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Ko, Hyang-Mi AU - Ko HM AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Boerner, Scott L AU - Boerner SL AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Hwang, David M AU - Hwang DM AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. FAU - Leighl, Natasha B AU - Leighl NB AD - Division of Hematology and Oncology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Medicine, University of Toronto, Toronto, Ontario, Canada. FAU - Tsao, Ming-Sound AU - Tsao MS AUID- ORCID: 0000-0002-9160-5405 AD - Laboratory Medicine Program, Department of Pathology, Princess Margaret Cancer Centre and University Health Network, Toronto, Ontario, Canada. AD - Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. LA - eng GR - Princess Margaret Cancer Foundation/ PT - Journal Article DEP - 20190807 PL - United States TA - Cancer JT - Cancer JID - 0374236 RN - 0 (Biomarkers, Tumor) RN - EC 2.7.10.1 (EGFR protein, human) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I) RN - EC 2.7.11.30 (TGFBR1 protein, human) SB - IM MH - *Biomarkers, Tumor MH - Canada MH - Disease Progression MH - ErbB Receptors/genetics/metabolism MH - Female MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Lung Neoplasms/*diagnosis/*metabolism/pathology MH - Male MH - Neoplasm Staging MH - Prevalence MH - Prognosis MH - Receptor, Transforming Growth Factor-beta Type I/genetics/*metabolism OTO - NOTNLM OT - 5A4 OT - ALK OT - biomarker testing OT - immunohistochemistry OT - laboratory-developed test OT - lung adenocarcinoma EDAT- 2019/08/08 06:00 MHDA- 2020/05/27 06:00 CRDT- 2019/08/08 06:00 PHST- 2019/04/24 00:00 [received] PHST- 2019/07/01 00:00 [revised] PHST- 2019/07/05 00:00 [accepted] PHST- 2019/08/08 06:00 [pubmed] PHST- 2020/05/27 06:00 [medline] PHST- 2019/08/08 06:00 [entrez] AID - 10.1002/cncr.32422 [doi] PST - ppublish SO - Cancer. 2019 Nov 15;125(22):4043-4051. doi: 10.1002/cncr.32422. Epub 2019 Aug 7.