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.

Gene mutations in small-cell lung cancer (SCLC): Results of a panel of 6 genes in a cohort of Italian patients / Bordi, P.; Tiseo, M.; Barbieri, F.; Bavieri, M.; Sartori, G.; Marchetti, A.; Buttitta, F.; Bortesi, B.; Ambrosini-Spaltro, A.; Gnetti, L.; Silini, E. M.; Ardizzoni, A.; Rossi, G.. - In: LUNG CANCER. - ISSN 0169-5002. - 86:3(2014), pp. 324-328. [10.1016/j.lungcan.2014.10.002]

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

Bordi P.;Tiseo M.;Silini E. M.;
2014-01-01

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.
2014
Gene mutations in small-cell lung cancer (SCLC): Results of a panel of 6 genes in a cohort of Italian patients / Bordi, P.; Tiseo, M.; Barbieri, F.; Bavieri, M.; Sartori, G.; Marchetti, A.; Buttitta, F.; Bortesi, B.; Ambrosini-Spaltro, A.; Gnetti, L.; Silini, E. M.; Ardizzoni, A.; Rossi, G.. - In: LUNG CANCER. - ISSN 0169-5002. - 86:3(2014), pp. 324-328. [10.1016/j.lungcan.2014.10.002]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2862604
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