Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Prognostic Value of p53 Overexpression in Patients with Pathologic Stage I Non-small Cell Lung Cancer

제 1기 비소세포폐암 환자에서 p53 과발현과 예후의 관계

  • Um, Sang-Won (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kim, Hojoong (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Kwon, O Jung (Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Han, Joungho (Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine) ;
  • Shim, Young Mog (Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine)
  • 엄상원 (성균관대학교 의과대학 내과학교실) ;
  • 김호중 (성균관대학교 의과대학 내과학교실) ;
  • 권오정 (성균관대학교 의과대학 내과학교실) ;
  • 한정호 (삼성서울병원 호흡기내과 병리과학교실) ;
  • 심영목 (삼성서울병원 호흡기내과 흉부외과학교실)
  • Received : 2008.09.20
  • Accepted : 2008.10.08
  • Published : 2008.12.30
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Abstract

Background: Chromosome 17p allele losses and mutations of p53 gene are the most common genetic abnormalities in lung cancer. The purposes of this study were to evaluate the factors associated with p53 protein overexpression and to evaluate its prognostic value in patients with pathologic stage I non-small cell lung cancer (NSCLC). Methods: This is a retrospective review for the patients who underwent surgical resection at Samsung Medical Center between Jan 2003 and Jun 2004. Immunohistochemical staining for p53 protein was performed on tumor tissues from patients with lung cancer. The p53 overexpression was evaluated in relation to age, sex, smoking history, histology and pathologic stage by univariate and multivariate analyses. The disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were analyzed using the Kaplan-Meier methods and the differences in DFS, DSS and OS were assessed by using the log-rank tests. Results: A total of 125 patients were included in the analysis and a median frequency of p53 expression in tumor tissue was 10%. The p53 overexpression (${\geq}10%$) was more common in squamous cell carcinoma (66%) than in adenocarcinoma (38%, p=0.002). The p53 overexpression was more common in pathologic stage IB (59%) than in IA (38%, p=0.002). Patients with p53-overexpressing tumor (27 years) smoked more years compared with those without it (20 years, p=0.032). Smoking history ${\geq}25$ pack-years was more common in patients with p53 overexpression (58%) than in those without it (38%, p=0.024). In the multivariate analysis, only histology was significantly associated with p53 overexpression. However, there were no significant differences of DFS, DSS and OS in relation to p53 status. Conclusion: The p53 overexpression was associated with histology, pathologic stage and smoking history in patients with pathologic stage I NSCLC. However, the p53 overexpression was not associated with patient's survival.

연구배경: p53 유전자의 돌연변이가 모든 조직형의 폐암에서 가장 흔한 유전적 이상으로 알려져 있다. 이전의 연구에도 불구하고, 폐암 조직에서 p53 단백질의 과발현과 생존과의 관계에 대해서는 아직도 논란이 있다. 본 연구의 목적은 수술로 절제한 병리학적 병기 1기인 비소세포폐암 환자에서 p53 단백질 과발현과 관련된 임상적 특징을 평가하고, p53 단백질 과발현과 예후와의 관계를 평가하는 것이다. 방 법: 본 연구는 삼성서울병원에서 2003년 1월부터 2004년 6월까지 폐암으로 치료 받은 환자 중 병리학적 병기 제 1기의 비소세포폐암 환자를 대상으로 한 후향적 연구이다. 폐암 환자의 종양 조직을 이용하여 p53 단백질에 대한 면역조직화학 염색이 시행되었다. 성별, 연령, 흡연력, 조직형 및 병기 등의 임상적 특징들에 따른 p53 과발 현 여부를 단변량 및 다변량 분석으로 평가하였다. 한편, p53의 과발현 여부에 따른 DFS, DSS 및 OS은 Kaplan-Meier 방법으로 평가하였고, 군간 비교는 log-rank test를 이용하였다 결 과: 125명의 연구 대상 환자에서 p53 면역 염색양성 종양 세포 빈도의 중앙값은 10%였다. 편평세포암에서 p53 과발현(${\geq}10%$)의 빈도가 66%로 선암의 38%보다 통계적으로 유의하게 증가되어 있었다(p=0.002). 병리학적 병기가 IB인 경우 p53 과발현의 빈도가 59%로 IA의 38%보다 증가되어 있었다(p=0.024). 흡연의 기간은 p53이 과발현 된 경우(27년)에 그렇지 않은 경우(20년)보다 통계적으로 유의하게 길었다(p=0.032). 25갑년 이상의 흡연력도 p53이 과발현 된 경우(58%)에 그렇지 않은 경우(38%)보다 더 흔하게 관찰되었다(p=0.024). 다변량 분석에서 p53 과발현과 관련된 인자는 편평세포암의 조직형뿐인 것으로 평가 되었다(p=0.002). 한편, p53 과발현 여부에 따른 DFS, DSS 및 OS의 차이는 없었으며, 편평세포암과 선암의 세부 군 분석에서도 생존의 차이는 없었다. 결 론: 수술로 절제한 제 1기 비소세포폐암 조직에서 면역조직화학 염색으로 평가한 p53 과발현은 조직형, 병기 및 흡연력과 관련이 있었고, 다변량 분석에서 조직형만이 p53 과발현과 관련된 독립적 인자였다. 하지만, p53 과발현과 환자의 생존과는 관련이 없었다.

Keywords

References

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