Fiona H Blackhall1, Solange Peters1, Lukas Bubendorf1, Urania Dafni1, Keith M Kerr1, Henrik Hager1, Alex Soltermann1, Kenneth J O'Byrne1, Christoph Dooms1, Aleksandra Sejda1, Javier Hernández-Losa1, Antonio Marchetti1, Spasenija Savic1, Qiang Tan1, Erik Thunnissen1, Ernst-Jan M Speel1, Richard Cheney1, Daisuke Nonaka1, Jeroen de Jong1, Miguel Martorell1, Igor Letovanec1, Rafael Rosell1, Rolf A Stahel2. 1. Fiona H. Blackhall and Daisuke Nonaka, Manchester University and The Christie National Health Services Foundation Trust, Manchester; Keith M. Kerr, Aberdeen University Medical School, Aberdeen Royal Infirmary, Aberdeen, United Kingdom; Solange Peters and Igor Letovanec, Centre Hospitalier Universitaire Vaudois, Lausanne; Lukas Bubendorf and Spasenija Savic, Institute for Pathology, University Hospital Basel, Basel; Alex Soltermann and Rolf A. Stahel, University Hospital Zurich, Zurich, Switzerland; Urania Dafni, Frontier Science Foundation-Hellas and University of Athens, Athens, Greece; Henrik Hager, University Hospital, Aarhus, Denmark; Kenneth J. O'Byrne, St James's Hospital, Dublin, Ireland; Christoph Dooms, University Hospital KU Leuven, Leuven, Belgium; Aleksandra Sejda, Medical University of Gdansk, Gdansk, Poland; Javier Hernández-Losa, Vall d'Hebron University Hospital, Barcelona; Miguel Martorell, Universitat de Valencia and Hospital General Universitario de Valencia, Valencia; Rafael Rosell, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain; Antonio Marchetti, Center of Predictive Molecular Medicine, University Foundation, Chieti, Italy; Qiang Tan, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Erik Thunnissen, VU University Medical Clinic Center; Jeroen de Jong, Netherlands Cancer Institute, Amsterdam; Ernst-Jan M. Speel, Maastricht University Medical Centre, Maastricht, the Netherlands; and Richard Cheney, Roswell Park Cancer Institute, Buffalo, NY. 2. Fiona H. Blackhall and Daisuke Nonaka, Manchester University and The Christie National Health Services Foundation Trust, Manchester; Keith M. Kerr, Aberdeen University Medical School, Aberdeen Royal Infirmary, Aberdeen, United Kingdom; Solange Peters and Igor Letovanec, Centre Hospitalier Universitaire Vaudois, Lausanne; Lukas Bubendorf and Spasenija Savic, Institute for Pathology, University Hospital Basel, Basel; Alex Soltermann and Rolf A. Stahel, University Hospital Zurich, Zurich, Switzerland; Urania Dafni, Frontier Science Foundation-Hellas and University of Athens, Athens, Greece; Henrik Hager, University Hospital, Aarhus, Denmark; Kenneth J. O'Byrne, St James's Hospital, Dublin, Ireland; Christoph Dooms, University Hospital KU Leuven, Leuven, Belgium; Aleksandra Sejda, Medical University of Gdansk, Gdansk, Poland; Javier Hernández-Losa, Vall d'Hebron University Hospital, Barcelona; Miguel Martorell, Universitat de Valencia and Hospital General Universitario de Valencia, Valencia; Rafael Rosell, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain; Antonio Marchetti, Center of Predictive Molecular Medicine, University Foundation, Chieti, Italy; Qiang Tan, Shanghai Lung Cancer Center, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People's Republic of China; Erik Thunnissen, VU University Medical Clinic Center; Jeroen de Jong, Netherlands Cancer Institute, Amsterdam; Ernst-Jan M. Speel, Maastricht University Medical Centre, Maastricht, the Netherlands; and Richard Cheney, Roswell Park Cancer Institute, Buffalo, NY. rolf.stahel@usz.ch.
Abstract
PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.
PURPOSE: The prevalence of anaplastic lymphoma kinase (ALK) gene fusion (ALK positivity) in early-stage non-small-cell lung cancer (NSCLC) varies by population examined and detection method used. The Lungscape ALK project was designed to address the prevalence and prognostic impact of ALK positivity in resected lung adenocarcinoma in a primarily European population. METHODS: Analysis of ALK status was performed by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in tissue sections of 1,281 patients with adenocarcinoma in the European Thoracic Oncology Platform Lungscape iBiobank. Positive patients were matched with negative patients in a 1:2 ratio, both for IHC and for FISH testing. Testing was performed in 16 participating centers, using the same protocol after passing external quality assessment. RESULTS: Positive ALK IHC staining was present in 80 patients (prevalence of 6.2%; 95% CI, 4.9% to 7.6%). Of these, 28 patients were ALK FISH positive, corresponding to a lower bound for the prevalence of FISH positivity of 2.2%. FISH specificity was 100%, and FISH sensitivity was 35.0% (95% CI, 24.7% to 46.5%), with a sensitivity value of 81.3% (95% CI, 63.6% to 92.8%) for IHC 2+/3+ patients. The hazard of death for FISH-positive patients was lower than for IHC-negative patients (P = .022). Multivariable models, adjusted for patient, tumor, and treatment characteristics, and matched cohort analysis confirmed that ALK FISH positivity is a predictor for better overall survival (OS). CONCLUSION: In this large cohort of surgically resected lung adenocarcinomas, the prevalence of ALK positivity was 6.2% using IHC and at least 2.2% using FISH. A screening strategy based on IHC or H-score could be envisaged. ALK positivity (by either IHC or FISH) was related to better OS.
Authors: M von Laffert; P Schirmacher; A Warth; W Weichert; R Büttner; R M Huber; J Wolf; F Griesinger; M Dietel; C Grohé Journal: Pathologe Date: 2016-03 Impact factor: 1.011
Authors: Ameen Abdulla Salahudeen; Manali I Patel; Paul Baas; Walter J Curran; Jeffrey D Bradley; David R Gandara; Glenwood D Goss; Tony S Mok; Suresh S Ramalingam; Everett E Vokes; Shakun M Malik; Heather A Wakelee Journal: Clin Lung Cancer Date: 2016-06-27 Impact factor: 4.785
Authors: M Dietel; K Jöhrens; M V Laffert; M Hummel; H Bläker; B M Pfitzner; A Lehmann; C Denkert; S Darb-Esfahani; D Lenze; F L Heppner; A Koch; C Sers; F Klauschen; I Anagnostopoulos Journal: Cancer Gene Ther Date: 2015-09-11 Impact factor: 5.987
Authors: Jamie E Chaft; Ibiayi Dagogo-Jack; Fernando C Santini; Juliana Eng; Beow Y Yeap; Benjamin Izar; Emily Chin; David R Jones; Mark G Kris; Alice T Shaw; Justin F Gainor Journal: Lung Cancer Date: 2018-05-22 Impact factor: 5.705