ERK1/2和p-ERK1/2在胆管癌组织中的表达及临床意义

Expression and clinical significance of ERK1/2 and p-ERK1/2 in cholangiocarcinoma

目的检测细胞外信号调节激酶1/2(ERK1/2)和其磷酸化状态(p-ERK1/2)在胆管癌组织中的蛋白表达及临床意义。方法收集肝外胆管癌组织标本74例,正常胆囊结石胆囊管组织标本25例,应用SP免疫组化法检测ERK1/2和p-ERK1/2蛋白的表达情况;采用卡方检验分析ERK1/2和p-ERK1/2表达水平与临床指标关系;应用Kaplan-Meier法绘制生存曲线,单因素分析采用Kaplan-Meier模型,多因素分析采用COX比例风险模型。结果胆管癌组织中ERK1/2和p-ERK1/2蛋白表达阳性率分别为32.4%(24/74)和60.8%(45/74),均明显高于正常肝外胆管组织[16.0%(4/25)、24.0%(6/25)],差异均有统计学意义(P<0.05)。p-ERK1/2蛋白表达与淋巴结转移和肿瘤分化程度密切相关(P<0.05);p-ERK1/2阴性表达的肝外胆管癌患者总体生存期明显长于p-ERK1/2表达阳性的患者(P=0.034)。单因素分析发现,p-ERK1/2的表达、淋巴结有无转移、临床分期和肿瘤的分化程度均与患者预后相关(P<0.05),多因素分析证实p-ERK1/2的表达是影响预后的独立风险因素(P<0.05)。结论胆管癌组织存在ERK1/2和p-ERK1/2高表达;p-ERK1/2的表达与临床分期可作为胆管癌的预后因子。

Objective To study the expression of ERK1/2 and p-ERK1/2 in cholangiocarcinoma and its clinical significance. Methods ERK1/2 and p-ERK1/2 protein expression were detected in 74 cases of cholangiocarcinoma and 25 cases of normal bile ducts tissues using immunohistochemistry（SP method）. The correlations of expression of ERK1/2and p-ERK1/2 with the clinical index were detected by chi-square test. Survival probabilities were estimated by the Kaplan-Meier method and assessed by a Log-rank test. The Kapla-Meier model was used to analyze single factor.Cox＇s proportional hazard regression model was performed to evaluate the multi-factors. Results The positive expression rate of ERK1/2 and p-ERK1/2 in the cholangiocarcinoma tissues were 32.4%（24/74）, 60.8%（45/74）, which were significantly higher than those in normal bile ducts tissues [16.0%（4/25）, 24.0%（6/25）], the differences were statistically significant（P〈0.05）. The expression of p-ERK1/2 protein was associated with lymph node metastases state and differentiation level of tumor（P〈0.05）. The survival time in patients with p-ERK1/2 negative expression was longer than patients with positive expression（P = 0.034）. Single factor analysis showed that p-ERK1/2 expression, differentiated degree of tumor, lymphatic metastasis and clinical stages were connected with prognosis（ P〈0.05）. Multi-factor analysis proved that p-ERK1/2 expression and clinical stages could be regarded as independent risk factors of cholangiocarcinoma prognosis（P〈0.05）. Conclusion There are higher expression of ERK1/2 and p-ERK1/2in cholangioc arcinoma. p-ERK1/2 and clinical stages may be served as a prognostic factor in cholangiocarcinoma.