폐암 조직에서의 PTEN 발현 정도와 Gefitinib의 반응율과의 관계

Immunohistochemical Study of Phosphatase and Tensin Homolog Deleted on Chromosome Ten in Gefitinib Treated Nonsmall Cell Lung Cancer Patients

  • 이승룡 (고려대학교 의과대학 내과학교실) ;
  • 이주한 (고려대학교 의과대학 병리학교실) ;
  • 정진용 (고려대학교 의과대학 내과학교실) ;
  • 이경주 (고려대학교 의과대학 내과학교실) ;
  • 이승현 (고려대학교 의과대학 내과학교실) ;
  • 김세중 (고려대학교 의과대학 내과학교실) ;
  • 이은주 (고려대학교 의과대학 내과학교실) ;
  • 허규영 (고려대학교 의과대학 내과학교실) ;
  • 정기환 (고려대학교 의과대학 내과학교실) ;
  • 정혜철 (고려대학교 의과대학 내과학교실) ;
  • 이상엽 (고려대학교 의과대학 내과학교실) ;
  • 김제형 (고려대학교 의과대학 내과학교실) ;
  • 신철 (고려대학교 의과대학 내과학교실) ;
  • 심재정 (고려대학교 의과대학 내과학교실) ;
  • 인광호 (고려대학교 의과대학 내과학교실) ;
  • 강경호 (고려대학교 의과대학 내과학교실) ;
  • 유세화 (고려대학교 의과대학 내과학교실)
  • Lee, Sung Yong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Ju Han (Department of Pathology, College of Medicine, Korea University) ;
  • Jung, Jin Yong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Kyoung Ju (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Seung Hyeun (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kim, Se Joong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Eun Joo (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Hur, Gyu Young (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Jung, Ki Hwan (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Jung, Hye Cheol (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Lee, Sang Yeub (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kim, Je Hyeong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Shin, Chol (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Shim, Jae Jeong (Department of Internal Medicine, College of Medicine, Korea University) ;
  • In, Kwang Ho (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Kang, Kyung Ho (Department of Internal Medicine, College of Medicine, Korea University) ;
  • Yoo, Se Hwa (Department of Internal Medicine, College of Medicine, Korea University)
  • 투고 : 2005.01.26
  • 심사 : 2005.04.22
  • 발행 : 2005.05.30

초록

연구 배경 : Gefitinib은 경구용 상피세포 성장인자 수용체 억제제로서 주로 동양인, 여성, 비흡연가, 선암 세포형의 폐암 환자에서 반응율이 좋은 것으로 되어 있으나 그 정확한 기전에 대해 밝혀진 것을 없다. 최근 몇몇 보고에 의하면 병기가 진행된 폐암 세포에서 PTEN 발현이 감소되어 있었으며, 또한 PTEN 발현이 감소된 폐암 세포주에서 EGFR tyrosine kinase inhibitor의 반응율이 감소되었음을 보고한 논문들이 있다. 이에 저자들은 본원에서 비소세포 폐암으로 진단받고 표준 항암화학요법에 실패한 이후 gefitinib으로 치료받은 환자군의 폐조직을 대상으로 PTEN의 발현 정도를 조사하였으며, PTEN의 발현 정도와 임상병기, 치료반응율과의 상관관계에 대해 분석하였다. 대상 및 방법 : 2002년 1월부터 2004년 8월까지 본원에 내원하여 원발성 비소세포성 폐암 진단 받은 후 표준 항암 화학요법에 실패하고 gefitinib을 복용한 환자 38명 중 2개월 이상을 투여 받아 반응 정도를 평가가 가능한 환자로서 폐조직에 대해 PTEN 면역조직화학 염색 및 정량화를 시행할 수 있었던 22명의 환자들에 대해 환자들의 약제 반응율과 PTEN의 발현양상과의 관계에 대해 후향적으로 조사하였다. 결 과 : 평균 연령은 62세, 남녀의 비는 6.3:1이었으며, 조직 병리학적 분류는 편평상피암 32%, 선암 59%, 대세포암 등 기타가 9%였다. 병기는 I 병기 1례, II 병기 1례, III 병기 9례, IV 병기가 11례였다. ECOG performance status는 grade 0-1이 9명, 2가 11명, 3이 2명이었다. 조직 병리학적 분류에 따른 PTEN 발현의 유의한 차이는 없었다. 또한 TNM 병기 상승에 따른 PTEN 발현율과는 서로 통계적으로 유의한 차이가 없었다. 그 러나, 약제 반응을 보인 군에서 약제 반응을 보이지 않은 군보다 PTEN 발현율이 통계적으로 유의하게 높게 나타났다(p=0.039). 결 론 : 표준 항암 화학 요법에 실패하고 gefitinib을 복용한 비소세포 폐암 환자의 약제 반응율과 종양 억제 단백질인 PTEN의 발현율과 서로 상관관계가 있다.

Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

키워드

참고문헌

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