结直肠癌组织EGFR基因表达及其与临床意义的研究

Clinicopathological correlative analysis of epidermal growth factor receptor gene in colorectal carcinoma

目的：通过对结直肠癌上皮生长因子受体（epidermal growth factor receptor，EGFR）基因的表达及其在体细胞突变的研究，探讨EGFR基因的表达与临床病理特征的关系。方法：收集解放军总医院病理科2004～2006年手术治疗的675例结直肠癌患者的临床及病理资料，采用免疫组织化学法检测结直肠癌组织中EGFR基因的表达并探讨其与患者临床病理特征的关系。在上述病例中随机选取25例，其中5例经免疫组织化学染色显示EGFR表达呈强阳性，提取这25例石蜡组织DNA，进行PCR扩增并测序从而分析在结直肠癌中EGFR基因的突变情况。结果：免疫组化结果显示EGFR基因的阳性率为21．33％（144／675）。EGFR基因的表达与结直肠癌的肿瘤直径（Χ^2=0．0204，P=0。8836）、肠壁浸润深度（Χ^2=1．1286，P=0．2881）、淋巴结转移情况（Χ^2=0．0708，P=0．7902）及肿瘤的病理分期（Χ^2=5．3691，P=0．1467）无关，但与肿瘤的分化程度（Χ^2=5．7793，P=0．0162）、腹腔及远处转移情况（Χ^2=4．3983，P=0．0360）密切相关。25例结直肠癌中有1例显示EGFR基因存在错义突变，有5例显示同义突变。结论：EGFR基因的表达与结直肠癌的分化程度及远处转移有关，可辅助判断患者的预后和转移情况以及指导临床治疗。EGFR基因在结直肠癌的突变可能为低频率事件。

OBJECTIVE：To study the expression and somatic mutations of the epidermal growth factor receptor （EGFR） gene in colorectal carcinoma and explore the possible relationship between it and clinicopathological characteristics. METHODS： A total of 675 patients with colorectal cancer, which were treated surgically during a period from 2004 to 2006, were studied by immunohistochemistry and the expression of EGFR was analyzed with clinicopathological indices. Then EGFR mutation status was detected by DNA extraction and PCR-sequences in 25 cases of those patients with colorectal carcinomas, of which 5 cases were strong positive for EGFR expression by immunohistochemical technique. RESULTS： One hundred and forty-four in six hundred and seven- ty-five （144/675） cases of colorectal adenocarcinomas were positive for the expression of EGFR and the positive rate was 21.33 %. EGFR expression was significantly corresponding to the differentiation degree （Χ^2=5. 779 3, P=0. 016 2） of the tumor and abdominal or distant metastases （Χ^2=4. 398 3, P= 0. 036 0）. There was no significant relationship between the expression of EGFR and the tumor size （Χ^2 =0. 020 4, P=0. 883 6）, infiltration （Χ^2= 1.128 6, P=0.288 1）, lymphatic invasion （Χ^2= 0.0708, P= 0.790 2） and TNM stage （Χ^2 = 5.369 1, P=0. 146 7）. Somatic EGFR mutations were identified in 1 of 25 colorectal carcinoma patients and 5 of the patients existed silent mutations. CONCLUSIONS： It is suggested that the expression of EGFR is related to the differentiation degree of the tumor and abdominal or distant metastases, therefore it can be helpful to predict the prognosis of the colorectal adenocarcinorna patients and provide information for further diagnosis and therapy. Somatic mutations on EGFR may be a low frequency event in colorectal cancer.