title: Analysis of the frequency of EGFR, KRAS and ALK mutations in patients with lung adenocarcinoma in Croatia.
abstract: BACKGROUND
  Many studies have been published on the mutational status of patients with lung adenocarcinomas, and great population-based variability in mutation frequencies has been reported. The main objective of the present study was to analyze the EGFR, KRAS and ALK mutation status in a representative cohort of patients in Croatia with lung adenocarcinomas and to correlate the mutational status with clinical data.
  
  
  METHODS
  All patients who were newly diagnosed within 6 months with histologically proven primary lung adenocarcinomas were included. Mutational analyses for EGFR and KRAS mutations were performed in a cobas z 480 analyzer. ALK immunohistochemistry was performed using the D5F3 clone on Benchmark XT instrument. Clinical data were obtained from the medical records.
  
  
  RESULTS
  Of the 324 patients, 59.9 % were male. At the time of diagnosis, the patients ranged in age range from 35 to 88 years (median 63 years). Most of the patients were current smokers or former smokers (77.2 %). EGFR mutations were found in 15.7 % of the patients, and of these mutations, exon 19 deletion was the most common (45.1 %). KRAS mutations were present in 34.9 % of the patients, while 4.1 % of patients were ALK-positive. The statistical significance of the presence of mutations was detected for both gender and smoking.
  
  
  CONCLUSIONS
  The detected mutation rates demonstrated a slightly higher prevalence of KRAS mutations, but not a higher prevalence of EGFR mutations or ALK gene rearrangement, in comparison with the rates found in other European countries. EGFR and ALK mutational status showed a statistically significant correlation with gender as well as with smoking, while KRAS mutation status showed a statistically significant correlation only with smoking.
authors.affiliation: Institute of Pathology, Medical University of Graz, Auenbruggerplatz 25, 8036, Graz, Austria. luka.brcic@medunigraz.at.|Institute of Pathology, University of Zagreb School of Medicine, Zagreb, Croatia. luka.brcic@medunigraz.at.
authors.forename: Luka
authors.initials: L
authors.lastname: Brcic
authors.affiliation: Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Jakopovic
authors.affiliation: Institute of Pathology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Misic
authors.affiliation: Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Fran
authors.initials: F
authors.lastname: Seiwerth
authors.affiliation: Cytology and Pathology Laboratory, University Clinic of Respiratory and Allergic Diseases, Golnik, Slovenia.
authors.forename: Izidor
authors.initials: I
authors.lastname: Kern
authors.affiliation: Clinical Department of Pathology and Cytology, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Silvana
authors.initials: S
authors.lastname: Smojver-Jezek
authors.affiliation: Institute for Medical Informatics, Statistics and Documentation Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Quehenberger
authors.affiliation: Department for Respiratory Diseases Jordanovac, University of Zagreb School of Medicine, University Hospital Centre Zagreb, Zagreb, Croatia.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Samarzija
authors.affiliation: Institute of Pathology, University of Zagreb School of Medicine, Zagreb, Croatia.
authors.forename: Sven
authors.initials: S
authors.lastname: Seiwerth
keywords: ALK; EGFR; Gender; KRAS; Lung adenocarcinoma; Smoking