[2004] The Performance of an L858R Mutation Specific EGFR Antibody in Non-Small Cell Lung Cancer Specimens

Ainura Kyshtoobayeva, Kenneth J Bloom. 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. Currently mutational status is assessed by sequencing of the EGFR gene or allele specific PCR. Approximately one third of EGFR mutations are the L858R substitution. We sought to assess the performance of an L858R EGFR mutation specific antibody.
Design: 100 formalin fixed embedded tissue sections, 50 harboring the L858R substituion and 50 assessed as non-mutated or harboring a mutation other than L858R were pulled from our archives. 4 micron sections were stained with a rabbit monoclonal L858R mutation specific antibody, 42B2, (cell signalling, Danvers, MA) 1:50, following heat-induced epitope retrieval, 100o C, pH9, 20 minutes.
Results: All 50 NSCLC tumors harboring the L858R mutation, showed expression with the 42B2 antibody ranging from 1+ to 3+ expression. Expression was limited to tumor cells but occasionally extended to atypical cells lining alveolar spaces adjacent to tumor. No expression was noted in any of the tumors lacking the L858R mutation, including all non-mutated tumors as well as those tumors harboring a mutation other than L858R.
Conclusions: The rabbit monoclonal antibody 42B2, directed against the EGFR L858R substitution demonstrated 100% sensitivity and 100% specificity for the detecetion of the L858R substitution. The usefulness of this antibody is limited since only about one third of NSCLC demonstrating an EGFR mutation harbor an L858R substitution.
Category: Pulmonary

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 303, Tuesday Afternoon

 

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