Experimental Research Center, Laboratory for Pancreatic Diseases, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, China.
Hum Pathol. 2013 Jan;44(1):69-76. doi: 10.1016/j.humpath.2012.04.014. Epub 2012 Aug 30.
Pancreatic cancer is a disease with poor prognosis and high mortality. To identify novel molecular markers that could predict the prognosis of pancreatic ductal adenocarcinoma, a total of 114 pancreatic ductal adenocarcinomas and 99 peritumoral tissues were collected. Protein levels of cleaved caspase-3, cyclin D1, epidermal growth factor receptor and Her-2 (human epidermal growth factor receptor 2) were measured by immunohistochemistry. Molecular abnormalities of cyclin D1/q11, Her-2/q17, and epidermal growth factor receptor/p7 were detected using fluorescence in situ hybridization. Results demonstrated that the protein levels of cleaved caspase-3, epidermal growth factor receptor, Her-2, and cyclin D1 were significantly higher in pancreatic ductal adenocarcinoma than that in peritumoral tissues (P = .000). Significantly more amplifications of epidermal growth factor receptor, Her-2, and cyclin D1 were observed in pancreatic ductal adenocarcinoma patients than in peritumoral tissues. In addition, 51.8% of pancreatic ductal adenocarcinoma tumors showed polysomy 7, 50% showed polysomy 11, and 40.4% showed polysomy 17. However, no polysomy was observed in peritumoral tissues. Her-2 amplification and polysomy 17 significantly correlated with poor prognosis of pancreatic ductal adenocarcinoma (P = .008 and P = .005, respectively). Interestingly, only cleaved caspase-3 protein level significantly correlated with poor survival in pancreatic ductal adenocarcinoma patients (P = .000). We also observed significant correlations of cleaved caspase-3 level with epidermal growth factor receptor, Her-2, and cyclin D1 protein levels and the molecular abnormalities of Her-2 and cyclin D1. Conclusively, cleaved caspase-3 level is an ideal biomarker to predict prognosis in pancreatic ductal adenocarcinoma patients and might be a better target for pancreatic ductal adenocarcinoma treatment than epidermal growth factor receptor/Her-2 and cyclin D1.
胰腺癌是一种预后不良、死亡率高的疾病。为了鉴定可能预测胰腺导管腺癌预后的新型分子标志物，共收集了 114 例胰腺导管腺癌和 99 例癌旁组织。采用免疫组织化学法检测了 cleaved caspase-3、cyclin D1、表皮生长因子受体和 Her-2（人表皮生长因子受体 2）的蛋白水平。应用荧光原位杂交检测了 cyclin D1/q11、Her-2/q17 和表皮生长因子受体/p7 的分子异常。结果表明，cleaved caspase-3、表皮生长因子受体、Her-2 和 cyclin D1 的蛋白水平在胰腺导管腺癌中明显高于癌旁组织（P=0.000）。在胰腺导管腺癌患者中，表皮生长因子受体、Her-2 和 cyclin D1 的扩增明显多于癌旁组织。此外，51.8%的胰腺导管腺癌肿瘤表现为 7 号染色体三体、50%表现为 11 号染色体三体、40.4%表现为 17 号染色体三体，而癌旁组织无三体。Her-2 扩增和 17 号染色体三体与胰腺导管腺癌的不良预后显著相关（P=0.008 和 P=0.005）。有趣的是，只有 cleaved caspase-3 蛋白水平与胰腺导管腺癌患者的不良生存显著相关（P=0.000）。我们还观察到 cleaved caspase-3 水平与表皮生长因子受体、Her-2 和 cyclin D1 蛋白水平以及 Her-2 和 cyclin D1 的分子异常显著相关。总之，cleaved caspase-3 水平是预测胰腺导管腺癌患者预后的理想标志物，可能是比表皮生长因子受体/Her-2 和 cyclin D1 更好的胰腺导管腺癌治疗靶点。
