The Significance of Ku70 Expression in Patients with Nasopharyngeal Carcinoma

비인강암에서 방사선치료의 예측인자로써 Ku70 발현의 의의

  • Song Si Yeol (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lee Sang-wook (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Yu Eunsil (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Cho Kyung-Ja (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Park Jin-hong (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim Sang Yoon (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Nam Soon Yuhl (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Lee Bong-Jae (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Kim Sung Bae (Department of Otorhinolaryngology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Choi Seung-Ho (Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Ahn Seung Do (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Shin Seong Soo (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center) ;
  • Choi Eun Kyung (Department of Radiation Oncology, University of Ulsan College of Medicine, Asan Medical Center)
  • 송시열 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 이상욱 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 유은실 (울산대학교 의과대학 서울아산병원 병리과) ;
  • 조경자 (울산대학교 의과대학 서울아산병원 병리과) ;
  • 박진홍 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 김상윤 (울산대학교 의과대학 서울아산병원 이비인후과) ;
  • 남순열 (울산대학교 의과대학 서울아산병원 이비인후과) ;
  • 이봉재 (울산대학교 의과대학 서울아산병원 이비인후과) ;
  • 김성배 (울산대학교 의과대학 서울아산병원 종양내과) ;
  • 최승호 (울산대학교 의과대학 서울아산병원 이비인후과) ;
  • 안승도 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 신성수 (울산대학교 의과대학 서울아산병원 방사선종양학과) ;
  • 최은경 (울산대학교 의과대학 서울아산병원 방사선종양학과)
  • Published : 2005.03.01

Abstract

Purpose : The objective of this study was to determine whether the expressions of the two components of DNA-dependent protein kinase, Ku70 and DNA-PKcs, influence the response to radiotherapy (RT) and outcome of treatment of non-disseminated nasopharyngeal carcinoma (NPC) in patients who received definitive RT. Materials and Methods : Sixty-six patients with NPC who were treated with radiotherapy alone or with concurrent chemotherapy between June 1995 and December 2001 were divided into groups based on the levels of immunoreactivity for Ku70 and DNA-PKcs in pretreatment biopsy specimens. The over-expression of Ku70 or DNA-PKcs groups Included patients whose biopsy specimens showed at least 50% immunopositive tumor cells; patients in which less than 50% of the tumor cells in the biopsy tissues were immunopositive were placed in the low Ku70 and DNA-PKcs groups. The immunoreactivities for Ku70 and DNA-PKcs were retrospectively compared with the sensitivity of the tumor to radiation and the patterns of therapy failure. Univariate analyses were peformed to determine the prognostic factors that influenced locoregional control of NPC. Results : The five-year locoregional control rate was significantly higher in the low Ku70 group (Ku(-)) (85%) than in the high Ku70 group (Ku(+)) (42%) (p=0.0042). However, there were no differences in the metastases-free survival rates between the two groups (Ku70 (+), 82%; Ku70 (-), 78%; p=0.8672). Univariate analysis indicated that the over-expression of Ku70 surpassed other well-known predictive clinocopathologic parameters as an Independent prognostic factor for locoregionai control. Eighteen of 22 patients who had locoregional recurrences of the tumor displayed an over-expression of Ku70. No significant association was found between the level of DNA-PKcs expression and the clinical outcome. Conclusion : Our data suggest that the level of Ku70 expression can be used as a molecular marker to predict the response to RT and the locoregional control after RT and concurrent chemotherapy in patients with non-disseminated NPC.

목적 : 방사선치료를 시행 받은 비인강암 환자에서 Ku70과 DNA-PKcs의 발현 정도가 국소제어율과 치료 실패 양상에 미치는 영향을 알아보고자 하였다. 대상 및 방법 : 1995년 6월부터 2001년 12월까지 서울아산병원에서 방사선치료 단독 또는 동시항암화학-방사선치료를 시행 받은 66명의 원격전이가 없는 비인강암 환자를 후향적으로 분석하였다. 진단 시 얻은 조직검사 표본에서 Ku70과 DNA-PKcs의 면역활성도를 분류하였는데, 그 기준은 면역활성도가 50% 이상 Ku (+)과, 50% 미만 Ku (-) 이었다. Ku70과 DNA-PKcs의 면역활성도와 방사선치료에 대한 종양의 반응 정도와 재발양상과의 상관관계를 알아보았으며, 비인강암의 국소제어율에 영향을 미치는 예후인자를 알아보기 위하여 단변량분석을 시행하였다. 결과 : Ku (-) 환자에서 Ku (+) 환자보다 높은 5년 국소제어율(85% vs. 42%, p=0.042)을 보였으나, 원격전이율은 두 집단간에 차이를 보이지 않았다(78% vs. 82%, p=0.8672). 단변량분석결과 Ku70의 과발현이 기존에 알려진 비인강암의 예후인자보다 우위에 있음을 알 수 있었다. 국소재발을 보였던 22명의 환자 중 18명의 환자에서 Ku70 (+)으로 관찰되었다. DNA-PKcs의 발현 정도는 방사선치료 결과에 영향을 미치지 않는 것으로 나타났다. 결론 : Ku70은 원격전이가 없는 비인강암 환자에서 방사선치료 단독 또는 동시항암화학-방사선치료 시행 이후 종양의 반응과 국소제어율을 예측할 수 있는 분자생물학적인 예측인자로 사용될 수 있을 것으로 생각한다.

Keywords

References

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