EGFR Mutation Rates in 18246 Consecutive Non-Small Cell Lung Cancer Samples
Kenneth J Bloom, Paul Choppa. Clarient, A GE Healthcare Company, Aliso Viejo, CA
Background: Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Two-thirds of patients present with advanced disease and have an average survival of less than 1 year with standard chemotherapy. Studies have demonstrated that exon 19 deletion or L858R substitution in the EGFR gene are the most powerful predictive biomarkers in patients treated with erlotinib or gefitinib. This has led to the recommendation that EGFR mutational status be evaluated prior to initiating chemotherapy. We sought to determine the frequency and distribution of EGFR mutations in our laboratory over the past several years.
Design: From June 2009 to October 2011 we have evaluated the mutational status of EGFR in 18246 formalin fixed paraffin embedded non-small cell lung cancer samples using an allele specific PCR procedure that is capable of detecting 29 of the most prevalent mutations in exons 18-21 of EGFR, (QIAGEN EGFR PCR kit). The assay uses a real-time PCR platform and is capable of detecting mutations at a sensitivity of 1-5% in a background of non-mutated alleles.
Results: Mutations were identified in 2435 (13.3%) of NSCLC samples tested. Of the 2435 samples with a detectable mutation 1252 (51.41%) harbored exon 19 deletions, 84 (3.45%) were mutations at codon 719, 80 (3.29%) were insertions in exon 20, 827 (33.96%) were L858R, 80 (3.29%) were L861Q, 25 (1.03%) were S768I, 24 (0.986%) were T790M, 2 (0.082%) 19 deletion + L858R, 3 (0.12%) exon 19 deletion + T790M, 19 (0.78%) L858R + T790M, 1 (0.041%) T790M + L861Q, 5 (0.21%) T790M + G719, 8 (0.33%) L858R + S768I, 1 (0.041%) L861Q + S768I, 19 (0.78%) S768I + G719 and 5 (0.21%) L861Q + G719.
Conclusions: Analysis of over 18,000 consecutive non-small cell lung cancer specimens sent to our laboratory for evaluation of EGFR mutation status demonstrated that 13.3% harbored an EGFR mutation as detected by our allele specific PCR procedure. Approximately half, (51.4%) harbored an exon 19 deletion and about one third (33.96%) demonstrated the L858R substitution, while 2.6% revealed multiple mutations in the EGFR gene. This represents the largest analysis of EGFR mutational status in a US based population to date.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 305, Tuesday Afternoon