Gene mutations in small-cell lung cancer (SCLC): Results of a panel of 6 genes in a cohort of Italian patients

Abstract Background No target therapies are presently available in the treatment of small-cell lung cancer (SCLC). We investigated the presence of potentially drugable mutations in the EGFR , c-MET , BRAF, KRAS , PDGFRa and c-KIT genes in a retrospective series of SCLC from 2 Italian Institutions. Correlations with immunohistochemical, clinical and outcome features were evaluated. Materials and methods Genes were studied by direct sequencing of DNA extracted from formalin-fixed paraffin-embedded tissues. Immunohistochemical expression of TTF-1, p63, chromogranin, synaptophysin, CD56 and bcl-2 was assessed. Results Samples from 113 SCLC patients were analyzed. All cases were wild-type for BRAF, KRAS , PDGFRa and c-KIT (data available for 82 patients). Two (1.8%) patients were EGFR -mutated (exon 19 delE746-A750 and exon 21 L858R); both were females, non-smoker and had limited disease. Overall survival of EGFR -mutated patients was 21 months as compared to 11 months in wild-type. Five (4.4%) patients were c-MET -mutated (4 on exon 14: 2 R988C, 1 D990N, 1 D102Y; 1 on exon 17 R1166Q); all were smokers, 3 were males and 4 had extensive disease. Their OS was comparable to wild-type cases (12 vs. 11 months). EGFR and c-MET mutations were mutually exclusive. Gene mutations did not correlate with immunophenotype. Conclusions Targetable mutations are uncommon in SCLC. EGFR -mutated patients tended to be female and non-smoker and experienced a prolonged OS suggesting a possible positive prognostic effect. c-MET mutations did not affect survival. Target therapy might be considered in EGFR and c-MET -mutated patients.