Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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PNA-Mediated PCR Clamping for the Detection of EGFR Mutations in Non-Small Cell Lung Cancer

비소세포폐암에서 PNA-Mediated PCR Clamping을 이용한 EGFR 돌연변이 분석법

  • Lee, Kye-Young (Department of Internal Medicine, Konkuk University School of Medicine) ;
  • Kim, Hee-Joung (Department of Internal Medicine, Konkuk University School of Medicine) ;
  • Kim, Sun-Jong (Department of Internal Medicine, Konkuk University School of Medicine) ;
  • Yoo, Gwang-Ha (Department of Internal Medicine, Konkuk University School of Medicine) ;
  • Kim, Won-Dong (Department of Internal Medicine, Konkuk University School of Medicine) ;
  • Oh, Seo-Young (Department of Pathology, Konkuk University School of Medicine) ;
  • Kim, Wan-Seop (Department of Pathology, Konkuk University School of Medicine)
  • 이계영 (건국대학교 의학전문대학원 내과학교실) ;
  • 김희정 (건국대학교 의학전문대학원 내과학교실) ;
  • 김순종 (건국대학교 의학전문대학원 내과학교실) ;
  • 유광하 (건국대학교 의학전문대학원 내과학교실) ;
  • 김원동 (건국대학교 의학전문대학원 내과학교실) ;
  • 오서영 (건국대학교 의학전문대학원 병리학교실) ;
  • 김완섭 (건국대학교 의학전문대학원 병리학교실)
  • Received : 2010.09.03
  • Accepted : 2010.10.15
  • Published : 2010.10.30
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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.

Keywords

References

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