Radiation Oncology Journal

The Korean Society for Radiation Oncology (대한방사선종양학회)
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MDM2, p53 and pRb Expression Prior to Definitive Chemoradiotherapy in Esophageal Carcinoma

식도암에서 MDM2, p53, pRb 발현과 동시적 항암화학방사선요법의 결과

  • Yoon, Mee-Sun (Departments of Radiation Oncology, Chonnam National University Medical School) ;
  • Lee, Jae-Hyuk (Departments of Pathology, Chonnam National University Medical School) ;
  • Cho, Sang-Hee (Departments of Internal Medicine, Chonnam National University Medical School) ;
  • Song, Ju-Young (Departments of Radiation Oncology, Chonnam National University Medical School) ;
  • Ahn, Sung-Ja (Departments of Radiation Oncology, Chonnam National University Medical School) ;
  • Chung, Ik-Joo (Departments of Internal Medicine, Chonnam National University Medical School) ;
  • Chung, Woong-Ki (Departments of Radiation Oncology, Chonnam National University Medical School) ;
  • Nah, Byung-Sik (Departments of Radiation Oncology, Chonnam National University Medical School) ;
  • Nam, Taek-Keun (Departments of Radiation Oncology, Chonnam National University Medical School)
  • 윤미선 (전남대학교 의과대학 방사선종양학교실) ;
  • 이재혁 (전남대학교 의과대학 병리학교실) ;
  • 조상희 (전남대학교 의과대학 혈액종양학교실) ;
  • 송주영 (전남대학교 의과대학 방사선종양학교실) ;
  • 안성자 (전남대학교 의과대학 방사선종양학교실) ;
  • 정익주 (전남대학교 의과대학 혈액종양학교실) ;
  • 정웅기 (전남대학교 의과대학 방사선종양학교실) ;
  • 나병식 (전남대학교 의과대학 방사선종양학교실) ;
  • 남택근 (전남대학교 의과대학 방사선종양학교실)
  • Published : 2007.12.30
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Abstract

Purpose: This study evaluated the pretreatment expression patterns of MDM2, p53, and pRb proteins to determine if the expression patterns could predict the outcome of concurrent chemoradiotherapy (CCRT) for esophageal squamous cell carcinoma and aid in the decisions for the selection of treatment modalities. Materials and Methods: Fifty-one patients that were treated with definitive chemoradiotherapy for stage $I{\sim}IVa$ esophageal squamous cell carcinoma were selected for this study. Radiotherapy was administered with daily $1.8{\sim}2\;Gy$ fractions up to a median dose of 54 Gy for primary tumors, and with four cycles of cisplatin/5-fluorouracil chemotherapy that was administered every 4 weeks, the first two cycles of which were administered concurrently with radiotherapy. Expression of MDM2, p53, and pRb was investigated by immunohistochemical analysis using pretreatment biopsy specimens. Results: MDM2, p53, and pRb were detected with high immunoreactivity in 19.6%, 27.5%, and 66.7% of the patients, respectively. However, there was no significant correlation between expression of these factors and clinical outcome. By the use of multivariate analysis with nine covariates-age, tumor location, tumor length, stage, pathological response, clinical response, MDM2 expression, p53 expression, and pRb expression, only pathological response and stage were significant factors for cause-specific survival. Conclusion: Expression of MDM2, p53, and pRb was not found to be clinically significant for predicting outcomes after CCRT in this study. Further studies with a larger patient population and longer follow-up periods are needed to re-evaluate the expression pattern and to identify new predictors for CCRT response.

목적: 식도암에서 동시적 항암화학방사선치료 전 MDM2, p53, pRb 발현양상이 치료반응 및 생존율 등 치료결과와 연관성이 있는지 알아보고자 하였다. 대상 및 방법: AJCC 병기 $I{\sim}IVa$로 근치적 목적의 동시적 항암화학방사선요법을 받은 51명의 환자를 대상으로 하였다. 방사선치료는 일일 $1.8{\sim}2.0$ Gy씩 원발병소에 중앙값 54 Gy를 시행하였고 항암화학요법은 CDDP/5-FU를 4주 간격으로 4회 시행하고 첫 2회는 방사선치료와 동시에 시행하였다. MDM2, p53, pRb 발현의 검출은 치료 전 내시경하 조직생검을 이용하여 면역조직화학 염색방법을 이용하였다. 단백발현 양성종양세포가 50%이상인 경우를 고발현군으로 정의하였다. 전체 환자의 중앙 추적관찰기간은 26개월이었다. MDM2, p53, pRb 고발현군은 각각 19.6%, 27.5%, 66.7% 이었다. 그러나 이들의 발현 정도와 치료반응, 종양특이 생존율, 전체 생존율 등 모두 유의한 연관성은 없었다. 연령(65세 이하 vs. 초과), 종양의 위치(상부, 중앙부, 하부),종양의 길이(5 cm이하 vs. 초과). 병기($I{\sim}II$ vs. $III{\sim}IVa$), MDM2 (저발현 vs. 고발현), p53 (저발현 vs. 고발현), pRb (저발현 vs. 고발현), 병리학적 완전관해여부, 임상적 완전관해여부 등 9개 요인들을 대상으로 종양특성 생존율에 대한 다변량 분석에서 병리학적 완전관해여부(RR 12.100, p<0.001)와 병기(RR 3.300, p=0.028) 만이 유의한 인자들이었다. 결 론: 본 연구에서 MDM2, p53, pRb의 치료 전 발현양상과 치료결과와 의미있는 연관성은 발견할 수 없었다. 향후 상기 발현인자들을 포함하여 잠재적인 예후인자로서 새로운 다른 발현인자들을 발굴하고 보다 많은 증례 수를 대상으로 추적기간을 보강하여 이들을 재평가하는 연구가 요망된다.

Keywords

References

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