Korean Journal of Clinical Laboratory Science (대한임상검사과학회지)

Korean Society for Clinical Laboratory Science (대한임상검사과학회)
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EGFR Analysis in Cytologic Samples of Lung Adenocarcinoma by Microdissection

미세 절제에 의한 폐 선암 세포 검체에서 EGFR 분석

  • Han, Jeong Yeon (Department of Pathology, Seoul National University Hospital) ;
  • Lee, Hoon Taek (Department of Animal Biotechnology, College of Animal Bioscience & Technology, Konkuk University) ;
  • Oh, Seo Young (Department of Pathology, Konkuk University Medical Center)
  • 한정연 (서울대학교병원 병리과) ;
  • 이훈택 (건국대학교 동물생명공학과) ;
  • 오서영 (건국대학교병원 병리과)
  • Received : 2015.06.09
  • Accepted : 2015.07.07
  • Published : 2015.09.30
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Abstract

The discovery of activating mutations in EGFR in a subset of lung adenocarcinomas was a major advance in our understanding of lung adenocarcinoma biology, and has led to groundbreaking studies that have demonstrated the efficacy of tyrosine kinase inhibitor therapy. Cytologic specimen procedures have become increasingly popular for obtaining diagnostic material in lung carcinomas. However, frequently the small amount of material or sparseness of tumor cells obtained from cytologic preparations limit the number of specialized studies, such as mutation analysis, that can be performed. In this study we used microdissection to isolate small numbers of tumor cells to assess for EGFR mutations from 76 cytological smear slides of patients with lung adenocarcinomas. We compared our results with previous molecular assays that had been performed on either surgical or cytology specimens as part of the patient's initial clinical work-up. Not only were we able to detect the identical EGFR mutation through the pyrosequencing, but we were also able to consistently detect the mutation from as few as 25 microdissected tumor cells. Furthermore, isolating a purer population of tumor cells resulted in increased sensitivity of mutation detection as we were able to detect mutations from microdissection-enriched cases. Therefore, microdissection can not only significantly increase the number of lung adenocarcinoma patients that can be screened for EGFR mutations, but can also facilitate the use of cytologic samples in the newly emerging field of molecular-based personalized therapies.

폐 선암의 일부에서 EGFR 돌연변이 활성화의 발견은 폐 선암의 생물학적 이해와 티로신 키나아제 억제제 치료에 대한 획기적인 연구에 중요하다. 세포 검체 검사는 폐암 진단에 중요한 역할을 하고 있으나 세포 검체로 부터 얻은 종양세포가 소량으로 돌연변이검사 및 다른 전문연구의 시행에 제한적이다. 본 연구에서는 폐선 암으로 알려진 76명의 환자로부터 얻은 세포슬라이드에서 미세절제기법을 통해 소량의 종양세포를 분리한 후 EGFR 돌연변이 검사를 시행하였다. 본 연구 결과는 이전 초기임상 진단의 일환으로 세포 및 조직으로 시행되었던 EGFR 돌연변이 검사 결과와 비교 분석하였다. 미세절제 기법으로 분리된 모든 종양세포는 파이로시퀀싱을 통하여 EGFR 돌연변이 분석이 가능했을 뿐만 아니라 25개의 종양세포에서도 EGFR 돌연변이 분석이 가능했다. 또한, 돌연변이 분석에서 미세절제기법을 통해 순수한 종양세포의 양을 증가시킨 검체에서 돌연변이 검출 감도가 증가하였다. 따라서, 미세절제기법은 세포 검체로 EGFR 돌연변이 분석을 시행 할수 있는 폐 선암 환자의 수를 증가시킬 뿐만 아니라 폐 선암 환자의 분자기반 맞춤치료에 세포 검체가 용이하게 사용될 수 있다.

Keywords

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