P53 Overexpression and Outcome of Radiation Therapy in Head & Neck Cancers

국문 초록 (Abstract)

목 적:실험적으로 p53 종양억제유전자는 세포의 방사선에 대한 반응을 조절하는 것으로 알려져 있는데, 임상에서 p53의 변화와 방사선치료 후의 예후와의 상호관련성은 아직 명확하게 규명되지 않은 상태이다. 이에 두경부종양환자에서 흔히 관찰되는 p53의 변화가 방사선치료결과에 어떤 영향을 미칠 수 있는지를 알아보고자 하였다.
재료 및 방법:두경부종양으로 진단되어 근치적 방사선치료를 받은 55명의 환자를 대상으로 임상결과를 후향적으로 분석하였다. 각 환자의 치료전 종양조직의 paraffin section을 human p53단백질에 대한 monoclonal antibody (D-07)로 면역조직화학염색하여 labeling Index (number of labelded nuclei/total number of counted nuclei x100)를 구하여, 임상결과와 연관지어 분석하였다.
결 과:전체환자의 67.2%에서 p53의 기능이상을 시사하는 과발현 소견을 보였다. 원발병소에 따른 과발현 빈도는 oral cavity, larynx, hypopharynx, nasopharynx순으로 각각 100%, 76%, 67%, 67%, 38%로 나타났다. 흡연자가 비흡연자에 비해 유의하게 높은 과발현 빈도를 보였다 (78.6%, 30.8%). 원발병소, 병기 및 Karnofsky performance status가 방사선치료에 대한 반응율과 유의한 연관을 보였으며, p53의 과발현여부는 치료반응율에 유의한 영향을 미치지 못하는 것으로 나타났다. 무병생존율 및 전체생존율에 영향을 미치는 인자는 원발병소와 병기였고, p53의 과발현여부는 유의한 연관을 보이지 못하였다.
결 론:근치적 방사선치료를 받은 두경부종양 환자에서, 면역조직화학염색에 의한 p53의 과발현율은 원발병소, 병기 및 흡연여부와 유관하였으며, 과발현여부가 치료반응율 및 생존율에 유의한 영향을 미치지 못하였다.

다국어 초록 (Multilingual Abstract)

Purpose:Experimental studies have implicated the wild type p53 in cellular response to radiation. Whether altered p53 function can lead to changes in clinical radiocurability remains an area of ongoing study. This study was performed to investigate whether any correlation between change of p53 and outcome of curative radiation therapy in patients with head and neck cancers.
Methods:Immunohistochemical analysis with a mouse monoclonal antibody (D0-7) specific for human p53 was used
to detect to overexpression of protein in formalin fixed, paraffin-embedded tumor sample from 55 head and neck
cancer patients treated with curative radiation therapy (median dose of 7020 cGy) from February 1988 to March 1996 at St. Mary's Hospital. Overexpression of p53 was correlated with locoregional control and survival using
Kaplan-Meier method. A Cox regression multivariate analysis was performed that included all clinical variables and status of p53 expression.
Results:Thirty-seven (67.2%) patients showed overexpression of p53 by immunohistochemical staining in their
tumor. One hundred percent of oral cavity, 76% of laryngeal, 66.7% of oropharyngeal, 66.7% of hypopharyngeal
cancer showed p53 overexpression (P=0.05). The status of p53 had significant relationship with stage of disease
(P=0.03) and history of smoking (P=0.001). The overexpression of p53 was not predictive of response rate to
radiation therapy. The locoregional control was not significantly affected by p53 status. Overexpression of p53 didn't have any prognostic implication for disease free survival and overall survival. Primary site and stage of disease were significant prognostic factors for survival.
Conclusions:The p53 overexpression as detected by immunohistochemical staining had significant correaltion with
stage, primary site of disease and smoking habit of patients. The p53 overexpression didn't have any predictive value for outcome of curative radiation therapy in a group of head and neck cancers.