Analysis of the frequency of oncogenic driver mutations and correlation with clinicopathological characteristics in patients with lung adenocarcinoma from Northeastern Switzerland

Alexandra Grosse,Markus Rechsteiner,Alex Soltermann,Claudia Grosse

doi:10.1186/s13000-019-0789-1

Alexandra Grosse, Markus Rechsteiner + Show 2 more

Open Access

https://doi.org/10.1186/s13000-019-0789-1

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Abstract

BackgroundMolecular testing of lung adenocarcinoma for oncogenic driver mutations has become standard in pathology practice. The aim of the study was to analyze the EGFR, KRAS, ALK, RET, ROS1, BRAF, ERBB2, MET and PIK3CA mutational status in a representative cohort of Swiss patients with lung adenocarcinoma and to correlate the mutational status with clinicopathological patient characteristics.MethodsAll patients who underwent molecular testing of newly diagnosed lung adenocarcinoma during a 4-year period (2014–2018) were included. Molecular analyses were performed with Sanger sequencing (n = 158) and next generation sequencing (n = 311). ALK, ROS1 and RET fusion gene analyses were also performed with fluorescence in situ hybridization and immunohistochemistry/immunocytochemistry. Demographic and clinical data were obtained from the medical records.ResultsOf 469 patients with informative EGFR mutation analyses, 90 (19.2%) had EGFR mutations. KRAS mutations were present in 33.9% of the patients, while 6.0% of patients showed ALK rearrangement. BRAF, ERBB2, MET and PIK3CA mutations and ROS1 and RET rearrangements were found in 2.6%, 1.9%, 1.9%, 1.5%, 1.7% and 0.8% of the patients, respectively. EGFR mutation was significantly associated with female gender and never smoking status. ALK translocations were more frequent in never smokers, while KRAS mutations were more commonly found in ever smokers. The association between KRAS mutational status and female gender was statistically significant only on multivariate analysis after adjusting for smoking.ConclusionThe EGFR mutation rate in the current study is among the higher previously reported mutation rates, while the frequencies of KRAS, BRAF, ERBB2 and PIK3CA mutations and ALK, ROS1 and RET rearrangements are similar to the results of previous reports. EGFR and KRAS mutations were significantly associated with gender and smoking. ALK rearrangements showed a significant association with smoking status alone.

Highlights

Molecular testing of lung adenocarcinoma for oncogenic driver mutations has become standard in pathology practice
The aim of the study was to analyze the frequencies of Anaplastic lymphoma kinase (ALK), ret proto-oncogene (RET) and ROS proto-oncogene 1 (ROS1) gene rearrangements and epidermal growth factor receptor gene (EGFR), Kirsten rat sarcoma (KRAS), B-Raf proto-oncogene (BRAF), erb-b2 receptor tyrosine kinase 2 gene (ERBB2), Mesenchymal epithelial transition protooncogene (MET) and Phosphatidylinositol-3 kinase catalytic subunit alpha (PIK3CA) mutations in a representative cohort of Swiss patients with lung adenocarcinoma using next generation sequencing (NGS) as testing method in the majority of cases and to correlate the molecular findings with clinicopathological patient characteristics
This study presents for the first time data on the EGFR, KRAS, ALK, ROS1, RET, BRAF, ERBB2, MET and PIK3CA mutation frequencies in a representative Swiss cohort of patients with stage I-IV lung adenocarcinoma using NGS

Summary

Introduction

Molecular testing of lung adenocarcinoma for oncogenic driver mutations has become standard in pathology practice. The aim of the study was to analyze the EGFR, KRAS, ALK, RET, ROS1, BRAF, ERBB2, MET and PIK3CA mutational status in a representative cohort of Swiss patients with lung adenocarcinoma and to correlate the mutational status with clinicopathological patient characteristics. Molecular testing for epidermal growth factor receptor gene (EGFR) mutations and ALK receptor tyrosine kinase (ALK) translocations has become the evidencebased standard of care for the management of advanced NSCLC. While a number of studies have already evaluated the frequencies of these genetic alterations in NSCLC patients from different countries, information on the prevalence of oncogenic driver mutations in the Swiss population are scarce and limited to population based epidemiological data derived from cancer registries and molecular test results based exclusively on Sanger sequencing rather than generation sequencing (NGS) [5, 6]

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