Samejima R, Kitajima Y, Yunotani S, Miyazaki K
Department of Surgery, Saga Medical School, Japan.
Anticancer Res. 1999 Nov-Dec;19(6C):5515-21.
Chemoradiotherapy is currently performed on patients with advanced esophageal squamous cell carcinoma (SCC). The preoperative administration revealed that the patients who responded well to chemoradiotherapy had favorable outcomes, whereas the poor responders conversely resulted in worse prognosis. The aim of this study was to identify molecular markers predicting sensitivity to chemoradiotherapy prior to this treatment.
Our clinical protocol for chemoradiotherapy for esophageal SCC were enrolled in 34 patients comprising 20 patients who underwent surgery after neoadjuvant chemoradiotherapy and 14 patients who were treated chemoradiotherapy without surgery. The expressions of cyclin D1, p53 and Ki-67 were investigated immunohistochemically in biopsy specimens obtained before the treatment from all 34 patients. The immunoreactivities were compared with responsiveness to chemoradiotherapy as evaluated by macroscopic or microscopic method.
The mean rate of primary tumor reduction as estimated by esophagography was 75.3% in the cyclin D1 negative group whereas 42.7% reduction rate was observed in the cyclin D1 positive group. The difference in the reduction rate between cyclin D1 positive and negative groups was statistically significant (p = 0.0025). The immunoreactivities of p53 and Ki-67 did not show a significant correlation with responsiveness to chemoradiotherapy. In neoadjuvant group, patients with cyclin D1-positive tumors showed significantly worse overall survival than patients with cyclin D1-negative tumors (p = 0.0380).
Among 34 patients with esophageal SCC, differences in the responsiveness to chemoradiotherapy were correlated with cyclin D1 immunoreactivity assessed in the biopsy specimens. Thus the cyclin D1 protein may be a useful predictor of sensitivity to concurrent chemoradiotherapy for esophageal SCC.
目前，晚期食管鳞状细胞癌（SCC）患者需接受放化疗。术前给药显示，对放化疗反应良好的患者预后良好，而反应不佳者则预后较差。本研究的目的是在放化疗前确定预测放化疗敏感性的分子标志物。
我们针对食管SCC的放化疗临床方案纳入了34例患者，其中20例在新辅助放化疗后接受手术，14例接受单纯放化疗。对所有34例患者治疗前活检标本进行免疫组织化学检测，研究细胞周期蛋白D1、p53和Ki-67的表达。将免疫反应性与通过宏观或微观方法评估的放化疗反应性进行比较。
食管造影估计，细胞周期蛋白D1阴性组原发肿瘤缩小平均率为75.3%，而细胞周期蛋白D1阳性组缩小率为42.7%。细胞周期蛋白D1阳性组与阴性组缩小率差异具有统计学意义（p = 0.0025）。p53和Ki-67的免疫反应性与放化疗反应性无显著相关性。在新辅助治疗组中，细胞周期蛋白D1阳性肿瘤患者的总生存期明显低于细胞周期蛋白D1阴性肿瘤患者（p = 0.0380）。
在34例食管SCC患者中，放化疗反应性差异与活检标本中评估的细胞周期蛋白D1免疫反应性相关。因此，细胞周期蛋白D1蛋白可能是食管SCC同步放化疗敏感性的有用预测指标。
