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目的探讨表皮生长因子受体(epidermal growth factor receptor,EGFR)在胃癌中的表达及其与临床病理参数、预后及多药耐药蛋白P-糖蛋白(P-glycoprotein,P170)、DNA拓扑异构酶Ⅱ(topoisomeraseⅡ,TopoⅡ)和谷胱苷肽-S转移酶(glutathione S-transferase-π,GST-π)表达的关系及意义。方法采用免疫组化ABC法检测160例胃癌组织中EGFR、P170、TopoⅡ及GST-π的表达以及EGFR在20例癌旁正常组织中的表达。研究EGFR在胃癌及癌旁正常黏膜中的表达差异,同时分析各因子表达与患者临床病理资料、预后的关系。结果 EGFR在160例胃癌标本中89例阳性,在20例癌旁正常黏膜中2例弱阳性,其在胃癌中的表达明显高于癌旁正常对照组(P<0.05)。EGFR与TopoⅡ的表达呈正相关(P<0.05)。EGFR表达与肿瘤的远处转移相关(P<0.05)。P170表达与肿瘤直径、淋巴结转移、远处转移及TNM分期相关(P<0.05)。GST-π表达与肿瘤远处转移及TNM分期相关(P<0.05)。TopoⅡ表达与病理分级、侵袭深度、远处转移及TNM分期相关(P<0.05)。单因素分析发现患者年龄、肿瘤直径、肿瘤部位、病理分级、侵袭深度、淋巴转移、远处转移、TNM分期、EGFR、TopoⅡ、GST-π均与预后有关(P<0.05)。Cox风险模型多因素分析发现病理分级、TNM分期、EGFR是影响胃癌预后的独立因素(P<0.05)。结论 EGFR在胃癌中高表达,与多药耐药蛋白TopoⅡ表达相关,是预测肿瘤预后的独立因素,可能参与化疗耐药。针对EGFR的分子靶向治疗可能使化疗或辅助化疗耐药,EGFR阳性胃癌患者获得较好的疗效。
Objective To investigate the expression of epidermal growth factor receptor (EGFR) in gastric cancer and its relationship with clinicopathological parameters, prognosis and the expression of P-glycoprotein (P170), DNA topoisomerase Topoisomerase Ⅱ (TopoⅡ) and glutathione S-transferase-π (GST-π) expression and its significance. Methods The expressions of EGFR, P170, TopoⅡ and GST-π in 160 cases of gastric cancer and the expression of EGFR in 20 cases of normal tissues were detected by immunohistochemical ABC method. To study the difference of EGFR expression in gastric cancer and adjacent normal mucosa, and to analyze the relationship between the expression of EGFR and clinical pathological data and prognosis. Results EGFR was detected in 89 of 160 gastric cancer specimens, and 2 of 22 adjacent normal mucosa tissues were weakly positive. The expression of EGFR in gastric cancer tissues was significantly higher than that in adjacent normal tissues (P <0.05). There was a positive correlation between EGFR and TopoⅡ (P <0.05). The expression of EGFR was correlated with distant metastasis (P <0.05). The expression of P170 was correlated with tumor diameter, lymph node metastasis, distant metastasis and TNM staging (P <0.05). The expression of GST-π was correlated with distant metastasis and TNM stage (P <0.05). Topo Ⅱ expression was correlated with pathological grade, invasion depth, distant metastasis and TNM stage (P <0.05). Univariate analysis showed that age, tumor diameter, tumor location, pathological grade, depth of invasion, lymph node metastasis, distant metastasis, TNM stage, EGFR, TopoⅡ and GST-π were all associated with prognosis (P <0.05). Cox risk model multivariate analysis found that pathological grade, TNM stage, EGFR is an independent factor affecting the prognosis of gastric cancer (P <0.05). Conclusion EGFR is highly expressed in gastric cancer, which is related to the expression of multidrug resistance protein Topo Ⅱ. It is an independent predictor of tumor prognosis and may be involved in chemoresistance. Targeted EGFR targeted therapy may make chemotherapy or adjuvant chemotherapy resistant, EGFR positive gastric cancer patients get better curative effect.