[1936] Microarray Evaluation of Epidermal Growth Factor Receptor (EGFR) Mutation Status

DR LaFrance, M Lowery-Nordberg. LSUHSC-Shreveport, Shreveport, LA; Feist-Weiller Cancer Center, Shreveport, LA

Background: With the advent of tyrosine kinase inhibitors and the promotion of individualized cancer therapy, stratification of patients with non-small cell lung carcinoma (NSCLC) has moved to the forefront of lung cancer chemotherapy. Molecular studies reveal polysomy for chromosome 7 (location of EGFR gene) in many solid tumors, and have implicated the importance of EGFR amplification in tumorigenesis. Additionally, the association of EGFR amplification with cytogenetic abnormalities in other tumor markers suggests diffuse genomic instability. Interestingly, however, patients with activating EGFR mutations have a genetically simpler disease that responds to targeted treatment and has a more favorable clinical outcome. The significance of diagnostic and therapeutic information provided by EGFR mutation status as determined by fluorescence in situ hybridization (FISH) has been previously documented by our group (Wei et al. Mod Pathol. 2007; 20(9):905-13). Presently, we will evaluate the DNA microarray platform as a novel method for documenting EGFR mutation status in patients with NSCLC.
Design: Unstained slides for 210 cases of NSCLC previously tested for EGFR amplification by FISH were collected from LSUHSC-Shreveport pathology archives. DNA was successfully extracted from 70 of these slides using the Pinpoint Slide DNA Isolation System (Zymo Research, Orange, CA). Using a multiplex microarray detection platform (Infiniti, AutoGenomics, Inc., Carlsbad, CA), the isolated DNA was analyzed for EGFR mutations in exons 18, 19, 20, and 21.
Results: EGFR mutation status was successfully determined by DNA microarray technology. Conclusive data was obtained in 38 of the 70 DNA samples isolated from unstained slides. A subset of the samples tested (11%) were positive for EGFR mutations, including two with exon 19 mutations, and two with mutations in exon 20.
Conclusions: The ability to identify which NSCLC patients harbor EGFR mutations is key to the strategic planning of oncology treatment. We propose a novel method whereby clinically significant EGFR mutations can be identified via a pre-therapeutic screening test. If positive for activating EGFR mutations, cancer patients can then be more successfully treated with targeted pharmaceuticals, such as gefitinib and erlotinib. In addition to facilitating the medical goal of individualized cancer therapy, this data may also be used to support preliminary data regarding the utility of biomarkers and other clinical indicators in prognostication and diagnosis of NSCLC.
Category: Techniques

Monday, March 22, 2010 1:00 PM

Poster Session II # 245, Monday Afternoon

 

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