Abstract

BackgroundFrequencies of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) have predominantly been determined in East Asian and North American populations, showing large differences between these populations. The aim of the present study was to determine the frequency of EGFR and KRAS mutations in NSCLC in the West European Dutch population in primary carcinomas and different metastatic locations.Methods EGFR (exons 19, 20 and 21) and KRAS (exons 2 and 3) mutation test results of NSCLC samples of patients in 13 hospitals were collected. The tests were performed on paraffin-embedded tissue or cytological material of primary and metastatic lung carcinomas.Results EGFR mutations were detected in 71/778 (9.1 %) tested patients; in 66/620 (10.6 %) adenocarcinomas. EGFR mutations were significantly more often detected in female than in male patients (13.4 % vs. 5.5 %, p < 0.001). KRAS mutations were found in 277 out of 832 (33.3 %) tested patients; in 244/662 (36.9 %) adenocarcinomas. A significantly increased frequency of EGFR mutations was observed in patients with malignant pleural/pericardial effusions (26.5 %; odds ratio (OR) 2.80, 95 % confidence interval (CI) 1.22–6.41), whereas the frequency of KRAS mutations was significantly decreased (18.8 %; OR 0.35, 95 % CI 0.14–0.86).ConclusionsIn the investigated Dutch cohort, patients with malignant pleural/pericardial effusion of lung adenocarcinoma have an increased frequency of EGFR mutations. The overall frequency of EGFR mutations in lung adenocarcinomas in this West European population is within the frequency range of North American and South European populations, whereas KRAS mutation frequency is higher than in any population described to date.

Highlights

  • Non-small-cell lung cancer (NSCLC) often presents at an advanced stage with no options for curative treatment

  • Within the group of former and current smokers, the average number of packyears smoking history was significantly lower in epidermal growth factor receptor (EGFR) mutation positive compared to EGFR mutation negative patients (23.6 vs. 35.6, P00.031)

  • To our best knowledge this is the first study showing an association between EGFR mutation rate and metastatic location in patients with lung adenocaricnoma in the European population

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Summary

Introduction

Non-small-cell lung cancer (NSCLC) often presents at an advanced stage with no options for curative treatment. New therapies, targeting specific signaling pathways, have been developed over the last years These include the small-molecule tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib, blocking signaling through the epidermal growth factor receptor (EGFR). For the West European population the frequency of EGFR and KRAS mutations has not been studied in large numbers of patients. KRAS mutations in non-small cell lung cancer (NSCLC) have predominantly been determined in East Asian and North American populations, showing large differences between these populations. The aim of the present study was to determine the frequency of EGFR and KRAS mutations in NSCLC in the West European Dutch population in primary carcinomas and different metastatic locations

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