EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset

A subset of lung cancers harbors a small inversion within chromosome 2p, giving rise to a transforming fusion gene, EML4-ALK ( echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene ), which encodes an activated tyrosine kinase. We have earlier examined the presence of EML4-ALK by multiplex reverse transcription-polymerase chain reaction in 363 specimens of lung cancer, identifying 11 adenocarcinoma cases featuring the fusion gene. In this study, we clinicopathologically examined the characteristics of the EML4-ALK -positive cases, including the mutation status of EGFR , KRAS , and TP53 , and whether they were of thyroid transcription factor-1 (TTF-1) cell lineage or not. Of 11 patients, 4 (36%) with EML4-ALK -positive lung adenocarcinomas who were below 50 years of age were affected by these diseases, as compared with 12 of 242 patients (5.0%) with EML4-ALK -negative lung adenocarcinomas ( P =0.00038). EML4-ALK -positive lung adenocarcinomas were characterized by less-differentiated grade ( P =0.0082) and acinar-predominant structure ( P