Detection of EGFR gene mutations in non-small cell lung cancer: Lessons from a single-institution routine analysis of 1,403 tumor samples

Vallee,Audrey; Sagan,Christine; Le Loupp,Anne-Gaelle; Bach,Kalyane; Dejoie,Thomas; Denis,Marc   G.

doi:10.3892/ijo.2013.2056

Detection of EGFR gene mutations in non-small cell lung cancer: Lessons from a single-institution routine analysis of 1,403 tumor samples

Authors:
- Audrey Vallee
- Christine Sagan
- Anne-Gaelle Le Loupp
- Kalyane Bach
- Thomas Dejoie
- Marc G. Denis
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Affiliations: Department of Biochemistry, Nantes University Hospital, Nantes, France, Department of Pathology, Nantes University Hospital, Nantes, France
Published online on: August 7, 2013 https://doi.org/10.3892/ijo.2013.2056
Pages: 1045-1051
Copyright: © Vallee et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Activating mutations of the epidermal growth factor receptor (EGFR) in lung tumors are associated with a dramatic response to tyrosine kinase inhibitors. Therefore, routine analysis of pathological specimens is mandatory in clinical practice. We have prospectively tested tumors from Caucasian lung tumor patients between January 2010 and June 2012. DNA was extracted from formalin-fixed paraffin-embedded tissues following macrodissection. The p.L858R substitution was assessed by allele-specific PCR and exon 19 deletions by PCR and DNA fragment analysis. Using a robust process from patient sampling to screening methods, we analyzed samples from 1,403 patients. The EGFR status could be successfully determined for 1,322 patients. EGFR mutations were detected in 179 (13.5%) patients, with female and adenocarcinoma histology predominance. Mutated patients were significantly older than non‑mutated patients. Similar mutation rates were obtained with primary tumors and metastases, and with surgical resection, bronchial biopsies, CT-guided needle biopsies and transbronchial needle aspiration. The sensitivity of our assays allowed us to detect EGFR mutations in samples poor (<10%) in tumor cells. Finally, the mutation rate was much higher in tumors expressing the TTF-1 antigen (145/820; 17.7%) than in TTF-1 negative tumors (3/218; 1.4%). The results obtained through routine analysis of more than 1,300 samples indicated that all types of specimen can be analyzed without any significant bias. TTF-1 immunostaining may be used to predict negative EGFR mutation status.

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