Important clinic-pathological differences have been observed between the various ES subgroups: the ES5 was enriched for never smokers, while never smokers were rarely classified among ES1; EGFR mutations were frequent in the ES5, but rare in the ES1 group; KRAS-mutated adenocarcinomas were enriched in the ES4 [26]. This evidence concerns the gene EGFR and adenocarcinoma.