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J Thorac Oncol. 2011 Aug;6(8):1407-12. doi: 10.1097/JTO.0b013e31821d41af.

Higher dosage of the epidermal growth factor receptor mutant allele in lung adenocarcinoma correlates with younger age, stage IV at presentation, and poorer survival.

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  • 1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

Abstract

INTRODUCTION:

The clinical significance of epidermal growth factor receptor (EGFR) mutant allele specific imbalance (MASI) in lung adenocarcinomas is unknown.

METHODS:

EGFR MASI was characterized by sequencing electropherograms (SEs) and EGFR fluorescence in situ hybridization (FISH) in 96 prospectively tested lung adenocarcinoma patients with a median follow-up of 20 months (all cases were EGFR mutation-positive).

RESULTS:

In 25 cases, the mutant allele (MA) peak was higher than the wild-type allele (WA) peak, indicating the presence of EGFR MASI (25/96, 26%). The adenocarcinomas with EGFR MASI had a 4.4-fold higher average EGFR/Chromosome Enumeration Probe 7 ratio than carcinomas without MASI (7.9 ± 3.8 versus 1.8 ± 0.6, p = 0.01). A high degree of correlation between the MA/WA ratio (SE) and the EGFR/CEP7 ratio (FISH) (ρ = 0.757, p = 0.003) validated the quantitative nature of SE. Amplification was the most common mechanism of EGFR MASI (13/21, 62%). EGFR MASI was more commonly associated with exon 19 mutations than with exon 21 mutations (19/53, 36%, versus 6/43, 14%, p = 0.015, odds ratio [OR] = 3.4) and in patients younger than 65 years (17/46, 37%, versus 8/50, 16%, p = 0.019, OR = 3.1). Patients with EGFR MASI presented with stage IV disease more frequently (p = 0.01, OR = 3.5) and had a poorer disease-specific survival rate (p = 0.021, 54% versus 83% at 31 months).

CONCLUSIONS:

EGFR MASI in lung adenocarcinomas can be assessed based on SE and can be used to identify younger patients with more aggressive disease.

PMID:
21587084
[PubMed - indexed for MEDLINE]
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