Journal of Chest Surgery

The Korean Society for Thoracic and Cardiovascular Surgery (대한심장혈관흉부외과학회)
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The Caspase-3 and c-myc Expressions in Completely Resected Non-small Cell Lung Cancer and Its Prognostic Significance

완전 절제된 원발성 비소세포 폐암에서 Caspase-3와 c-myc 단백의 발현과 임상 예후

  • Cho, Deog-Gon (Department of Thoracic and Cardiovascular Surgery, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Cho, Kyu-Do (Department of Thoracic and Cardiovascular Surgery, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Kang, Chul-Ung (Department of Thoracic and Cardiovascular Surgery, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Jo, Min-Seop (Department of Thoracic and Cardiovascular Surgery, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Yoo, Jin-Young (Department of Pathology, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Ahn, Myeong-Im (Department of Radiology, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Kim, Chi-Hong (Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Shim, Byoung-Yong (Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Kim, Sung-Whan (Department of Radiation Oncology, St. Vincent's Hospital, The Catholic University of Korea) ;
  • Kim, Hoon-Kyo (Department of Internal Medicine, St. Vincent's Hospital, The Catholic University of Korea)
  • 조덕곤 (가톨릭대학교 성빈센트병원 흉부외과학교실) ;
  • 조규도 (가톨릭대학교 성빈센트병원 흉부외과학교실) ;
  • 강철웅 (가톨릭대학교 성빈센트병원 흉부외과학교실) ;
  • 조민섭 (가톨릭대학교 성빈센트병원 흉부외과학교실) ;
  • 유진영 (가톨릭대학교 성빈센트병원 병리학교실) ;
  • 안명임 (가톨릭대학교 성빈센트병원 영상의학교실) ;
  • 김치홍 (가톨릭대학교 성빈센트병원 내과학교실) ;
  • 심병용 (가톨릭대학교 성빈센트병원 내과학교실) ;
  • 김성환 (가톨릭대학교 성빈센트병원 방사선종양학교실) ;
  • 김훈교 (가톨릭대학교 성빈센트병원 내과학교실)
  • Published : 2008.08.05
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Abstract

Background: Caspase-3 is a cysteine protease that plays a major role in the process of apoptotic cell death. The dysregulated expression of c-myc contributes to the tumorigenesis in a variety of human cancers. The aim of this study was to investigate the expressions of caspase-3 and c-myc and their significances as prognosis markers in patients with completely resected non-small cell lung cancer (NSCLC). Material and Method: A total 130 consecutive patients who had undergone complete resection without pre-operative radio-therapy or chemotherapy between May 1996 and December 2003 for NSCLC were retrospectively reviewed. The median follow-up period of the patients was 50 months (range: $3{\sim}128$ months). The expressions of caspase-3 and c-myc were immuno-histochemically examined, and these were correlated with the clinico-pathologic data. Result: The prevalence of caspase-3 and c-myc expressions in the patients was 68% (88/130) and 59% (77/130), respectively. Significant association was found between the frequency of the expressions of caspase-3 and c-myc (p=0.025). The caspase-3 and c-myc expressions were not significantly associated with the prognosis in all the patients. However, according to stages, a positive caspase-3 expression was significantly correlated with a favorable prognosis for patients with stage IIIa disease (median survival period: 35 months vs. 10 months, p=0.021). Multivariate analysis showed the pathologic stage to be significantly correlated with a good prognosis in all the patients (p=0.024), and with a positive caspase-3 expression, well differentiated tumor and negative neuronal invasion in the patients with stage llla disease (p=0.005, p=0.003, p=0.004, respectively). Conclusion: Caspase-3 and c-myc were frequently expressed in NSCLC, suggesting its possible involvement in tumor development. The caspase-3 expression, as determined with performing immunohistochemical staining, may be a favorable prognostic indicator in patients with completely resected NSCLC an advanced stage (IIIa).

배경: 인체에서 세포증식과 세포자멸사(apoptosis)과정에서의 불균형은 악성 종양의 발생과 그 예후에 중요하게 작용한다. 본 연구는 세포자멸사에 관계하는 세포내 신호전달 경로에 중요하게 작용하는 cysteine protease의 일종인 caspase-3 단백과 많은 종류의 암에서 세포분열 혹은 세포자멸사 모두에 관여하는 것으로 알려진 c-myc oncogene 단백의 발현과 폐암과의 연관성을 관찰하고, 완전 절제된 원발성 비소세포 폐암 환자에서 caspase-3와 c-myc 단백의 발현과 임상적인 예후 인자로서의 의의를 알아보고자 했다. 대상 및 방법: 1996년 5월부터 2003년 12월까지 원발성 비소세포 폐암으로 수술 전 항암화학요법이나 방사선 요법을 시행 받은 환자를 제외하고, 완전 절제술을 시행 받은 총 130명의 환자를 대상으로 하였다. 추적 조사 기간은 중앙값 50개월($3{\sim}128$개월)로 연구시점에서 수술후 최소 3년 이상 경과 된 환자를 대상으로 하였다. 폐암조직에서 caspase-3과 c-myc 단백의 발현은 면역조직화학적으로 염색하여 관찰하고 환자의 임상 및 병리 정보를 후향적으로 조사 비교하였다. 결과: Caspase-3와 c-myc 단백의 발현율은 각각 68% (88/130)과 59% (77/130)으로 caspase-3와 c-myc 단백의 발현율 사이에 유의한 상관 관계가 있었다(p=0.025). Caspase-3와 c-myc 단백의 발현 여부가 전체 수술 환자와의 생존율과의 관계에 유의한 차이는 없었지만, IIIa군 환자에서 caspase-3 단백의 발현과 생존율 간에 유의한 차이를 보였다(중앙생존기간 35 vs. 10개월, p=0.021). 다변량 분석에 의한 예후인자로 전체 대상환자에서 병리조직학적인 병기(p=0.024), IIIa군 환자에서 caspase-3 단백발현(p=0.005), 암세포 분화도가 좋은 경우(p=0.003), 그리고 암세포가 현미경학적으로 신경침습이 얼는 경우(p=0.004)에 좋은 예후를 보였다. 걸론: 비소세포 폐암에서 caspase-3와 c-myc 단백은 비교적 흔히 발현하고 폐암발생 과정에 관여하는 것으로 추정되며, 완전 절제된 진행성 병기(IIIa군)의 폐암 환자에서 면역조직화학염색법을 이용한 caspase-3 단백의 발현은 양호한 예후를 나타내는 임상적인 예후의 지표가 될 수 있다.

Keywords

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