TY - JOUR T1 - French multicentric validation of <em>ALK</em> rearrangement diagnostic in 547 lung adenocarcinomas JF - European Respiratory Journal JO - Eur Respir J SP - 207 LP - 218 DO - 10.1183/09031936.00119914 VL - 46 IS - 1 AU - Sylvie Lantuejoul AU - Isabelle Rouquette AU - Hélène Blons AU - Nolwenn Le Stang AU - Marius Ilie AU - Hugues Begueret AU - Valerie Grégoire AU - Paul Hofman AU - Audrey Gros AU - Stephane Garcia AU - Nathalie Monhoven AU - Mojgan Devouassoux-Shisheboran AU - Audrey Mansuet-Lupo AU - Françoise Thivolet AU - Martine Antoine AU - Jean-Michel Vignaud AU - Frederique Penault-Llorca AU - Françoise Galateau-Sallé AU - Anne McLeer-Florin Y1 - 2015/07/01 UR - http://erj.ersjournals.com/content/46/1/207.abstract N2 - 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 (&lt;15%). FISH was not interpretable for seven cases. ALK patients were young (p=0.003), mostly females (p=0.007) and light/nonsmokers (p&lt;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 &gt;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 ER -