Tuberc Respir Dis.  2010 Oct;69(4):271-278. 10.4046/trd.2010.69.4.271.

PNA-Mediated PCR Clamping for the Detection of EGFR Mutations in Non-Small Cell Lung Cancer

• Lee KY
• Kim HJ
• Kim SJ
• Yoo GH
• Kim WD
• Oh SY
• Kim WS

• KMID: 2114621
• DOI: http://doi.org/10.4046/trd.2010.69.4.271

Abstract

BACKGROUND
Recent studies have demonstrated that the epidermal growth factor receptor (EGFR) genotype is the most important predictive marker to EGFR-tyrosine kinase inhibitors (TKIs) and first-line gefitinib treatment will be approved in the near future for use in non-small cell lung cancer (NSCLC) patients with the EGFR mutation. Direct sequencing is known to be the standard for detecting EGFR mutations; however, it has limited sensitivity. Peptide nucleic acids (PNA)-mediated PCR clamping method is a newly introduced method for analyzing EGFR mutations with increased sensitivity and stability.
METHODS
A total of 71 NSCLC patients were analyzed for EGFR mutations using the PNA-mediated PCR clamping technique. Sixty-nine patients were analyzed for clinicopathologic correlation with EGFR genotype; 2 patients with indeterminate results were excluded. In order to determine EGFR-TKI drug response, 57 patients (42 gefitinib, 15 erlotinib) were included in the analysis.
RESULTS
The EGFR mutation rate was 47.8%. Being female, a non-smoker, and having adenocarcinoma were favorable clinicopathologic factors, as expected. However, more than a few smokers (33.3%), male (28.1%), and patients with non-adenocarcinoma (28.6%) had the EGFR mutation. Having a combination of favorable clinicopathologic factors did not increase the EGFR mutation rate significantly. Drug response to EGFR-TKIs showed significant differences depending on the EGFR genotype; ORR was 14.3% for wild type vs 69.0% for mutant type; DCR is 28.6% for wild type vs 96.6% for mutant type. The median EGFR-TKI treatment duration is 7.6 months for mutant type group and 1.4 months for wild type group.
CONCLUSION
EGFR genotype determined using the PNA-mediated PCR clamping method is significantly correlated with the clinical EGFR-TKI responses and PNA-mediated PCR.

Keyword

Peptide Nucleic Acids; Receptor, Epidermal Growth Factor; Carcinoma, Non-Small-Cell Lung

MeSH Terms

Adenocarcinoma
Carcinoma, Non-Small-Cell Lung
Constriction
Female
Genotype
Humans
Male
Mutation Rate
Peptide Nucleic Acids
Phosphotransferases
Polymerase Chain Reaction
Quinazolines
Receptor, Epidermal Growth Factor
Peptide Nucleic Acids
Phosphotransferases
Quinazolines
Receptor, Epidermal Growth Factor

Figure

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  Figure 1 The proportions of favorable clinicopathologic factors and each combination in EGFR mutation positive group (n=33).

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  Figure 2 Progression free survival (duration of EGFR-TKI treatment) according to EGFR genotype.

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