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


Journal

Diagnostic pathology
ISSN: 1746-1596
Titre abrégé: Diagn Pathol
Pays: England
ID NLM: 101251558

Informations de publication

Date de publication:
11 Feb 2019
Historique:
received: 13 11 2018
accepted: 01 02 2019
entrez: 13 2 2019
pubmed: 13 2 2019
medline: 14 6 2019
Statut: epublish

Résumé

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. All 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. Of 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. The 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.

Sections du résumé

BACKGROUND BACKGROUND
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.
METHODS METHODS
All 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.
RESULTS RESULTS
Of 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.
CONCLUSION CONCLUSIONS
The 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.

Identifiants

pubmed: 30744664
doi: 10.1186/s13000-019-0789-1
pii: 10.1186/s13000-019-0789-1
pmc: PMC6371584
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

18

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Auteurs

Alexandra Grosse (A)

Institute of Pathology and Molecular Pathology, Clinical Pathology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Claudia Grosse (C)

Institute of Pathology, Kepler University Hospital, Krankenhausstraße 9, 4021, Linz, Austria. claudiagrosse@gmx.at.

Markus Rechsteiner (M)

Institute of Pathology and Molecular Pathology, Diagnostic Molecular Pathology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

Alex Soltermann (A)

Institute of Pathology and Molecular Pathology, Clinical Pathology, University Hospital Zurich, Rämistrasse 100, 8091, Zurich, Switzerland.

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