title: 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.
  
  
  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.
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bordi
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Parma, Italy. Electronic address: mtiseo@ao.pr.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tiseo
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases Clinic, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Barbieri
authors.affiliation: Department of Oncology, Haematology and Respiratory Diseases Clinic, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Bavieri
authors.affiliation: Cervical Cancer Screening Unit, Department of Oncology and Advanced Technologies, Azienda St. Maria Nuova IRCCS, Reggio Emilia, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Sartori
authors.affiliation: Center of Predictive Molecular Medicine, Center of Excellence on Aging, University of Chieti, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Marchetti
authors.affiliation: Center of Predictive Molecular Medicine, Center of Excellence on Aging, University of Chieti, Italy.
authors.forename: Fiamma
authors.initials: F
authors.lastname: Buttitta
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Parma, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Bortesi
authors.affiliation: Pathology Unit, Central Hospital of Bolzano, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ambrosini-Spaltro
authors.affiliation: Section of Anatomy and Pathology, Azienda Ospedaliero-Universitaria, Parma, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Gnetti
authors.affiliation: Section of Anatomy and Pathology, Azienda Ospedaliero-Universitaria, Parma, Italy.
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Silini
authors.affiliation: Medical Oncology Unit, Azienda Ospedaliero-Universitaria, Parma, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
authors.affiliation: Operative Unit of Pathology, Azienda Ospedaliero-Universitaria Policlinico, Modena, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000096:biosynthesis / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020797:Receptor, Platelet-Derived Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met; D020797:Receptor, Platelet-Derived Growth Factor beta; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
keywords: BRAF; EGFR; Gene mutations; KRAS; PDGFRa; SCLC; c-KIT; c-MET