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目的 探讨食管上皮癌变过程中细胞周期调控因子cyclin E、CDK2和p21WAF1的表达状况及其意义。方法 应用免疫组化SP法和原位杂交方法分别检测48例食管癌组织、31例非典型增生组织和17例正常食管粘膜中cyclin E、CDK2和p21WAF1蛋白及mRNA表达。应用半定量RT PCR和Western blot检测22例新鲜食管癌及相应癌旁组织的mRNA和蛋白表达。结果 从食管正常粘膜、非典型增生组织到癌组织,cyclin E和CDK2蛋白和mRNA阳性表达率逐渐上升,差异具有统计学意义(P<0.01或P<0.05)。食管癌组织中cyclin E、CDK2和p21WAF1蛋白及mRNA高表达,与癌旁组织或切缘正常食管粘膜有显著性差异(P<0.01)。cyclin E、CDK2和p21WAF1 基因表达显著正相关(P<0.01 或P<0.05)。结论 食管上皮癌变过程中,细胞周期相关基因cyclin E和CDK2表达逐渐增强。cyclin E基因表达异常是食管癌变过程中的早期事件。p21WAF1 基因在食管癌中高表达,可能与细胞周期调控的反馈机制有关。
Objective To investigate the expression of cyclin E, CDK2 and p21WAF1 in esophageal carcinogenesis and its significance. Methods The expressions of cyclin E, CDK2 and p21WAF1 protein in 48 cases of esophageal cancer, 31 cases of atypical hyperplasia and 17 cases of normal esophageal mucosa were detected by immunohistochemical SP method and in situ hybridization. The mRNA and protein expressions of 22 fresh esophageal carcinomas and corresponding paracancerous tissues were detected by semi-quantitative RT-PCR and Western blot. Results The positive expressions of cyclin E and CDK2 protein and mRNA in esophageal normal mucosa, atypical hyperplasia tissues and cancerous tissues gradually increased, with statistical significance (P <0.01 or P <0.05). The expressions of cyclin E, CDK2 and p21WAF1 protein and mRNA in esophageal cancer tissues were significantly higher than those in adjacent normal tissues or normal esophageal mucosa (P <0.01). Cyclin E, CDK2 and p21WAF1 gene expression was significantly correlated (P <0.01 or P <0.05). Conclusion The expression of cyclin E and CDK2 in esophageal epithelial carcinogenesis gradually increases. Abnormal cyclin E gene expression is an early event in esophageal carcinogenesis. The high expression of p21WAF1 gene in esophageal cancer may be related to the feedback mechanism of cell cycle regulation.