结直肠癌组织中EGFR及HER-2的表达及临床意义

Expression of EGFR and HER-2 in colorectal carcinoma and their clinical significance

目的 探讨结直肠癌组织中表皮生长因子受体（epidermal growth factor receptor,EGFR）和人类表皮生长因子受体-2（human epidermal receptor-2,HER-2）蛋白的表达,并分析二者与临床病理特征的关系。方法 采用免疫组化PV-9000两步法检测78例结直肠癌组织中EGFR和HER-2的表达,分析二者表达与结直肠癌临床病理特征的关系;应用银染原位杂交（silverinsituhybridization,SISH）法检测结直肠癌组织中HER-2基因扩增情况。结果 EGFR在结直肠癌组织中的阳性率为69.23%（54/78）,EGFR表达与结直肠癌浸润深度、淋巴结转移呈正相关,与患者性别、年龄、肿瘤大小、细胞分化程度、Dukes分期无关;HER-2在结直肠癌组织中的阳性率为25.64%（20/78）,HER-2表达与结直肠癌浸润深度、淋巴结转移呈正相关,与患者性别、年龄、肿瘤大小、细胞分化程度、Dukes分期无关。EGFR与HER-2蛋白表达呈正相关。20例HER-2蛋白阳性者中,10例HER-2基因扩增;其中15例HER-2蛋白（＋＋～＋＋＋）中有10例HER-2基因扩增,占高表达组的66.67%;5例HER-2蛋白（＋）者无HER-2基因扩增。结论 EGFR和HER-2蛋白在结直肠癌中均呈高表达,EGFR和HER-2的表达与结直肠癌侵袭、转移密切相关,二者可能存在协同作用。HER-2蛋白（＋＋～＋＋＋）与HER-2基因扩增密切相关,故该类患者可考虑先行免疫组化初步筛选,再行SISH法检测确认,从而为结直肠癌分子的靶向治疗提供有价值的信息。

Purpose To explore the expression and clinical significance of epidermal growth factor receptor（ EGFR）and human epi-dermal receptor-2（HER-2）in colorectal carcinoma. Methods Immunohistochemistry（IHC）PV-9000 was used to detect the expres-sion of EGFR and HER-2 in 78 cases of colorectal carcinoma. Silver in situ hybridization（ SISH）was used to detect HER-2 amplifica-tion in colorectal carcinoma. Results The positive rates of EGFR in 78 colorectal carcinomas were 69. 23%（ 54/78 ）. The differ-ences of the expression of EGFR between different depth of invasion group and lymph node metastasis group were statistically signifi-cant. The differences of the expression of EGFR between different aging group,gender group,tumor size,different histological grading group and Dukes stage were insignificant. The positive rates of HER-2 in 78 cases of colorectal carcinoma were 25. 64%（20/78）. The differences of the expression of HER-2 between different depth of invasion group and lymph node metastasis group were statistically sig-nificant. The differences of the expression of HER-2 between different aging group,gender group,tumor size,histological grading group and Dukes stage were insignificant. The expression of EGFR and HER-2 was positively correlated. Among the 20 cases of HER-2 protein overexpression,10 cases showed HER-2 gene amplification,15 cases showed HER-2 protein overexpression（＋＋～＋＋＋）by IHC and 10 cases showed HER-2 gene amplification by SISH. The rate of HER-2 gene amplification was 66. 67%. 5 cases with low HER-2 protein overexpression（ ＋）and no case showed HER-2 gene amplification. Conclusions EGFR and HER-2 are highly ex-pressed in colorectal carcinoma. EGFR and HER-2 expression is connected to invasion and metastasis process of colorectal carcinoma. The both may be synergy. The correlation between HER-2 protein overexpression（＋＋～＋＋＋）and HER-2 gene amplification is statisti-cally significant. Therefore,immunohistochemistry can be regarded as an initial screening method for HER-2 gene amplification,and then SISH testing should be done as well to confirm the result. It is useful for molecular target therapy to detect HER-2 status in color-ectal carcinoma.