Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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The Clinical and Histopathologic Features according to Loss of LKB1 Protein Expression on Primary Lung Cancer

원발성 폐암에서 LKB1 단백질 발현 소실에 따른 임상 양상 및 조직병리학적 특성

  • Hwang, Ki Eun (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Jo, Hyang-Jeong (Department of Pathology, College of Medicine, Wonkwang University) ;
  • Lee, Kang Kyoo (Department of Therapeutic Radiology and Oncology, College of Medicine, Wonkwang University) ;
  • Sim, Hyeok (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Song, Jung Sup (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Shin, Jeong Hyun (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Shin, Seong Nam (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Park, Seong-Hoon (Department of Radiology, College of Medicine, Wonkwang University) ;
  • Hong, Kyeong-Man (Research Institute, National Cancer Center) ;
  • Park, Jung-Hyun (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Jeong, Jong-Hoon (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Kim, Hui Jung (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Kim, Hak-Ryul (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Yang, Sei-Hoon (Department of Internal Medicine, College of Medicine, Wonkwang University) ;
  • Jeong, Eun-Taik (Department of Internal Medicine, College of Medicine, Wonkwang University)
  • 황기은 (원광대학교 의과대학 내과학교실) ;
  • 조향정 (원광대학교 의과대학 병리학교실) ;
  • 이강규 (원광대학교 의과대학 방사선종양학교실) ;
  • 심혁 (원광대학교 의과대학 내과학교실) ;
  • 송정섭 (원광대학교 의과대학 내과학교실) ;
  • 신정현 (원광대학교 의과대학 내과학교실) ;
  • 신성남 (원광대학교 의과대학 내과학교실) ;
  • 박성훈 (원광대학교 의과대학 영상의학교실) ;
  • 홍경만 (국립암센터) ;
  • 박정현 (원광대학교 의과대학 내과학교실) ;
  • 정종훈 (원광대학교 의과대학 내과학교실) ;
  • 김휘정 (원광대학교 의과대학 내과학교실) ;
  • 김학렬 (원광대학교 의과대학 내과학교실) ;
  • 양세훈 (원광대학교 의과대학 내과학교실) ;
  • 정은택 (원광대학교 의과대학 내과학교실)
  • Received : 2007.12.24
  • Accepted : 2008.03.13
  • Published : 2008.05.30
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Abstract

Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.

연구배경: LKB1 (STK11)유전자는 Peutz-Jeghers syndrome에서 생식세포 돌연변이가 있으면 소화기와 폐를 포함한 타 장기의 암 발생 위험도가 증가한다고 알려져 있으며, 또한 종양 억제 기능이 있다고도 알려지고 있다. 하지만 현재까지 폐암에서 LKB1 유전자의 생물학적 기능이 명확하게 밝혀져 있지 않아, 저자들은 폐암조직에서 LKB1 단백질 발현소실과 임상양상 및 조직병리와의 연관관계를 알아보고자 하였다. 방법: 1998년 3월부터 2006년 3월까지 본원에 내원하여 원발성 폐암으로 진단받고 근치적 절제술을 시행 받은 77명의 환자를 대상으로 하였다. 파라핀에 포매된 조직을 택하여 면역조직화학염색법으로 LKB1 단백질 발현을 확인하였고, 정상 기관지 상피세포 세포질에서의 단백질 발현과 비슷한 정도의 발색을 갖는 종양세포가 전체 종양에서 30% 이상인 경우를 양성으로 판정하였다. 결과: LKB1 발현 양성은 40% (31/77)였고, 남성, 흡연, 편평상피암인 경우에 LKB1 발현 음성률이 통계적으로 유의하게 높았다. 종양위치가 중앙부위일수록 LKB1 발현 음성률이 증가하는 경향이 있으며, 종양 위치가 말초 부위인 경우 흡연력이 있는 군에서 LKB1 발현 음성률이 통계적으로 유의하게 높았다. TNM 병기가 진행할수록 LKB1 발현 음성률이 증가하는 경향이 있었으며, T2 병기 이상, N 병기가 진행할수록 LKB1 발현 음성률이 높아지는 경향이 있었으나, 통계적 유의성은 보이지 않았다. 결론: 원발성 폐암환자에서 LKB1 발현소실은 성별, 흡연력, 조직병리 형태와 의미있는 상관관계를 보였으나, 예후인자로서의 의의는 찾지 못했다. 하지만 환자의 숫자가 적어 추후의 연구가 이루어져야 할 것으로 사료된다.

Keywords

References

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