Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Utility of MAGE Gene Detection in Bronchial Washing Fluid for Patients with Peripheral NSCLC

말초 비소세포폐암 환자에서 기관지 세척액 MAGE 유전자 진단의 유용성

  • Kim, Suhyun (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Hojoong (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kwon, O Jung (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Chung, Man Pyo (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Suh, Gee Young (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Koh, Won-Jung (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Ham, Cho Rom (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Nam, Hae Seong (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Um, Sang-Won (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kwon, Yong Soo (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Park, Sung-Hoon (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 김수현 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 김호중 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 권오정 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 정만표 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 서지영 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 고원중 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 함초롬 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 남해성 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 엄상원 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 권용수 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과) ;
  • 박성훈 (성균관대학교 의과대학 내과학교실, 삼성서울병원 호흡기내과)
  • Received : 2007.12.11
  • Accepted : 2008.01.11
  • Published : 2008.01.30
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Abstract

Background: The melanoma antigen-encoding (MAGE) genes are known to be expressed in various cancer cells, including non-small cell lung cancer (NSCLC), and are silent in all normal tissues except for the testis. In patients with peripheral NSCLC, bronchial washing fluid can be used to detect the MAGE genes, suggesting a diagnosis of lung cancer. In order to evaluate the diagnostic utility of the MAGE test in patients with peripheral NSCLC, bronchial washing fluid was investigated in patients with peripheral pulmonary nodules, which were invisible as detected by bronchoscopy. Methods: Bronchial washing fluid from 37 patients was used for cytological examinations and MAGE gene detection, using RT-nested-PCR of common A1-A6 mRNA. Results were compared to a final diagnosis of patients as confirmed by pathology. Results: Among the 37 subjects, NSCLC was diagnosed in 21 patients, and benign pulmonary diseases were diagnosed in 16 patients. MAGE mRNA was detected in 10 of 21 (47.6%) NSCLC patients, while conventional cytology examinations were positive for MAGE expression in 2 of 21 (9.5%) cases. MAGE expression was observed in 4 of 16 (25%) benign pulmonary disease patients. Conclusion: The MAGE test of bronchial washing fluid can be used as a sensitive predictor of peripheral NSCLC patients.

연구배경: 기관지 내시경으로 조직 검사가 불가능한 고립성 폐결절 환자에서 경피적 폐생검이 중요한 진단 방법으로 사용되고 있으나, 기흉 및 출혈 등의 합병증 및 접근성 등이 문제가 된다. 흑색종항원유전자(Melanoma Antigen Gene, MAGE)는 악성 흑색종에서 처음 발견된 20 종양 항원 및 유전자로서, 비소세포폐암을 비롯한 다양한 암종에서 발현되며 정상 조직에서는 남성의 생식기 세포 및 태반에서만 발현된다. 본 연구는 기관지내시경으로 보이지 않았던 비소세포폐암 환자에서 기관지 세척액을 이용한 MAGE 양성 여부를 검사하여 폐암의 진단에 어느정도 도움이 되는지 알아보고자 하였다. 방법: 2007년 1월부터 2개월간 삼성서울병원 호흡기 내과에서 기관지 내시경을 시행한 환자 중에서 내시경적 조직 검사가 불가능한 고립성 폐결절 환자 37명을 대상으로 하였다. 기관지 세척을 시행하여 MAGE A1-6 RT-nested PCR (iC&G Co, Daegu, Korea)검사와 세포진 검사를 시행하였고, 경피적 폐생검 및 수술을 통한 병리학적인 진단과 비교하였다. 결과: 37명 중에서 비소세포폐암 환자는 21명(56.8%) 이었고(선암종 13/21, 편평상피세포암 8/21), 나머지 16명 (43.2%)은 폐결핵(5), 진균 감염(3), 기질화 폐렴(2) 및 유육종증, 비결핵 항산균 폐질환과 선천성 낭종 등으로 진단되었다. 비소세포폐암 환자에서 세포학적인 검사의 양성률은 9.5% (2/21)에 불과하였으나, MAGE mRNA는 47.6% (10/21)에서 양성을 보여 양성 예측률이 71.4%였다. MAGE 양성률은 편평상피세포암에서 더 높게 나타났다 (선암종 30.8%, 편평상피세포암 75.0%, p>0.05). 양성 병변으로 진단된 16명의 MAGE 발현율은 25.0% (4/16)였다. 결론: 기관지 세척액을 이용한 MAGE 검사는 기관지 내시경을 통한 조직검사가 불가능한 고립성 폐결절에서 기존의 세포진검사에 비해 우수한 양성 예측률을 나타내어 폐암의 진단에 도움이 될 것으로 보인다.

Keywords

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