RT Journal Article SR Electronic T1 French multicentric validation of ALK rearrangement diagnostic in 547 lung adenocarcinomas JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 207 OP 218 DO 10.1183/09031936.00119914 VO 46 IS 1 A1 Sylvie Lantuejoul A1 Isabelle Rouquette A1 Hélène Blons A1 Nolwenn Le Stang A1 Marius Ilie A1 Hugues Begueret A1 Valerie Grégoire A1 Paul Hofman A1 Audrey Gros A1 Stephane Garcia A1 Nathalie Monhoven A1 Mojgan Devouassoux-Shisheboran A1 Audrey Mansuet-Lupo A1 Françoise Thivolet A1 Martine Antoine A1 Jean-Michel Vignaud A1 Frederique Penault-Llorca A1 Françoise Galateau-Sallé A1 Anne McLeer-Florin YR 2015 UL http://erj.ersjournals.com/content/46/1/207.abstract AB Anaplastic lymphoma kinase (ALK) gene rearrangements in lung adenocarcinoma result in kinase activity targetable by crizotinib. Although fluorescence in situ hybridisation (FISH) is the reference diagnostic technique, immunohistochemistry (IHC) could be useful for pre-screening.Diagnostic yields of ALK IHC, FISH and quantitative reverse transcriptase PCR performed in 14 French pathology/molecular genetics platforms were compared. 547 lung adenocarcinoma specimens were analysed using 5A4 and D5F3 antibodies, two break-apart FISH probes and TaqMan kits. Clinicopathological data were recorded.140 tumours were ALK rearranged (FISH with ≥15% of rearranged cells) and 400 were ALK FISH negative (<15%). FISH was not interpretable for seven cases. ALK patients were young (p=0.003), mostly females (p=0.007) and light/nonsmokers (p<0.0001). 13 cases were IHC negative but FISH ≥15%, including six cases with FISH between 15% and 20%; eight were IHC positive with FISH between 10% and 14%. Sensitivity and specificity for 5A4 and D5F3 were 87% and 92%, and 89% and 76%, respectively. False-negative IHC, observed in 2.4% of cases, dropped to 1.3% for FISH >20%. Variants were undetected in 36% of ALK tumours.Discordances predominated with FISH ranging from 10% to 20% of rearranged cells and were centre dependent. IHC remains a reliable pre-screening method for ALK rearrangement detection.IHC is useful in pre-screening for ALK rearrangement, with FISH for confirmation of diagnosis http://ow.ly/Iuu5j