Paola Bordi1, Marcello Tiseo2, Fausto Barbieri3, Mario Bavieri3, Giuliana Sartori4, Antonio Marchetti5, Fiamma Buttitta5, Beatrice Bortesi1, Andrea Ambrosini-Spaltro6, Letizia Gnetti7, Enrico Maria Silini7, Andrea Ardizzoni1, Giulio Rossi8. 1. Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Parma, Italy. 2. Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Parma, Italy. Electronic address: mtiseo@ao.pr.it. 3. Department of Oncology, Haematology and Respiratory Diseases Clinic, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy. 4. Cervical Cancer Screening Unit, Department of Oncology and Advanced Technologies, Azienda St. Maria Nuova IRCCS, Reggio Emilia, Italy. 5. Center of Predictive Molecular Medicine, Center of Excellence on Aging, University of Chieti, Italy. 6. Pathology Unit, Central Hospital of Bolzano, Italy. 7. Section of Anatomy and Pathology, Azienda Ospedaliero-Universitaria, Parma, Italy. 8. Operative Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
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.
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 SCLCpatients 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.
Authors: Bradford J Siegele; Konstantin Shilo; Bo H Chao; David P Carbone; Weiqiang Zhao; Olga Ioffe; Wilbur A Franklin; Martin J Edelman; Dara L Aisner Journal: Lung Cancer Date: 2016-02-26 Impact factor: 5.705
Authors: Jin-Yan Liang; Fan Tong; Fei-Fei Gu; Yang-Yang Liu; Yu-Lan Zeng; Xiao-Hua Hong; Kai Zhang; Li Liu Journal: Medicine (Baltimore) Date: 2017-05 Impact factor: 1.889
Authors: Fatma Abdelraouf; Adam Sharp; Manisha Maurya; Debbie Mair; Andrew Wotherspoon; Alex Leary; David Gonzalez de Castro; Jaishree Bhosle; Ayatallah Nassef; Taghrid Gaafar; Sanjay Popat; Timothy A Yap; Mary O'Brien Journal: BMC Res Notes Date: 2015-11-18