Shinozaki H, Ozawa S, Ando N, Tsuruta H, Terada M, Ueda M, Kitajima M
Department of Surgery, Keio University, School of Medicine, 35 Shinano-machi, Shinjuku-ku, Tokyo 160, Japan.
Clin Cancer Res. 1996 Jul;2(7):1155-61.
The cyclin D1, referred to as PRAD-1, has been mapped to the 11q13 region, and its expression has been detected in squamous cell lines and several primary esophageal carcinomas. We assessed cyclin D1 amplification in 122 squamous cell carcinomas of the esophagus. Samples for DNA extraction were obtained from formalin-fixed paraffin-embedded specimens, and 10 microgram of each DNA sample were subjected to slot blot analysis. The presence of more than three gene copies was considered evidence of gene amplification. Amplification of cyclin D1 was detected in 28 (23%) of 122 cases of squamous cell carcinoma of the esophagus. There were no significant differences between the clinicopathological background factors in groups positive and negative for cyclin D1 amplification, but the survival rate of patients exhibiting amplification was significantly lower (P < 0.001). The groups were stratified according to the pN (pathological N category) factor and pT (pathological T category) factor in the TNM classification, and the cumulative survival rates in the amplification groups were always significantly lower. Amplification of cyclin D1 was correlated with distant organ metastasis after curative operations, but there was no significant difference in lymph node recurrence rates of patients with or without amplification. Cyclin D1 amplification had the second highest partial regression coefficient in the multivariate analysis, after the pN factor. Amplification of cyclin D1 was independent of the TNM classification as a prognostic factor, and was a useful marker for predicting outcome and distant organ metastasis in patients with squamous cell carcinoma of the esophagus. It appears that appropriate treatment can be selected by evaluating both TNM factors and cyclin D1 amplification.
细胞周期蛋白D1，又称为PRAD-1，已被定位于11q13区域，并且在鳞状细胞系和一些原发性食管癌中检测到其表达。我们评估了122例食管鳞状细胞癌中细胞周期蛋白D1的扩增情况。用于DNA提取的样本取自福尔马林固定石蜡包埋标本，每个DNA样本取10微克进行狭缝印迹分析。基因拷贝数超过三个被视为基因扩增的证据。在122例食管鳞状细胞癌中有28例（23%）检测到细胞周期蛋白D1扩增。细胞周期蛋白D1扩增阳性和阴性组的临床病理背景因素之间无显著差异，但扩增患者的生存率显著较低（P<0.001）。根据TNM分类中的pN（病理N分类）因素和pT（病理T分类）因素对组进行分层，扩增组的累积生存率始终显著较低。细胞周期蛋白D1扩增与根治性手术后远处器官转移相关，但扩增患者与未扩增患者的淋巴结复发率无显著差异。在多变量分析中，细胞周期蛋白D1扩增的偏回归系数仅次于pN因素，位居第二。细胞周期蛋白D1扩增作为一个预后因素独立于TNM分类，是预测食管鳞状细胞癌患者预后和远处器官转移的有用标志物。似乎通过评估TNM因素和细胞周期蛋白D1扩增可以选择合适的治疗方法。
