198例胃癌手术标本Her-2蛋白表达与临床病理的相关性和靶向治疗

Her-2 protein expression in 198 specimens of gastric cancer and its correlation with clinicopathologic features and targeted therapy

背景与目的:通过组织芯片(tissue microarry,T M A)和免疫组织化学(immunohistochemistry,IHC)技术检测人类表皮生长因子受体2(Human epidermal growth factor receptor 2,Her-2)在胃癌(gastric carcinoma,GC)中的表达,研究胃癌中Her-2表达的临床意义,为胃癌靶向治疗奠定理论基础。方法:构建包含198例胃癌组织和89例正常胃黏膜的组织芯片,应用免疫组化方法检测胃癌中Her-2蛋白的表达。分析Her-2表达与临床病理参数之间的相关性及其对预后的影响。结果:198例胃癌中男性147例,女性51例,男女比例为2.9∶1。患者年龄31～85岁,中位年龄66.5岁。按照Lauren's分型分为肠型169例,弥漫型29例。组织芯片免疫组化结果显示198例胃癌细胞中Her-2总表达率为32.8%,而正常胃黏膜无表达。Her-2表达与肿瘤大小、组织类型、肿瘤侵袭深度和TNM分期有关。肠型胃癌的表达率(36.7%)明显高于弥漫型胃癌(10.4%,P=0.005)。Her-2蛋白表达与患者性别、年龄、肿瘤部位及预后无关。结论:胃癌中Her-2蛋白的表达率为32%,其表达与胃癌的某些生物学行为有关。肠型胃癌Her-2蛋白表达率明显高于弥漫型胃癌。因此,肠型胃癌患者可能为曲妥珠单抗靶向治疗的主要群体,并有可能从辅助靶向治疗中获益。

Background and purpose：The purpose of this study was to detect the expression of human epidermal growth factor receptor 2（Her-2） in 198 cases of gastric carcinomas（GC） by using tissue microarray（TMA） and immunohistochemical（IHC） techniques,and to reveal the correlation between the expression of the Her-2 protein and clinicopathologic features of GC.This will theoretically aid in establishing the fundamentals molecular targeted therapy.Methods：The immunohistochemical method was used to detect the Her-2 protein status in gastric cancer for the purpose of constructing tissue microarray with 198 cases of GCs and 89 cases of gastric normal mucosa.Statistical analysis with SPSS 13.0 software was applied to assay the relationship between the Her-2 expressions and varied clinicopathologic parameters and prognosis.Results：Of 198 GCs,there were 147 males and 51 females.The ratio of male to female was 2.9∶1.The patients’ age ranged from 31 to 85 years,with a median of 66.5 years.According to the Lauren＇s classification of GC,there were 169 cases of intestinal types and 29 cases of diffuse types.Tissue microarray immunohistochemical staining results showed the total Her-2 expression rate in GC as 32.8%,but there was no expression in the normal control gastric mucosa.Her-2 expression statuses were significantly related to tumor size,histological type,Lauren’s classification,depth of tumor invasion,and TNM staging（P0.05）.The Her-2 expression percentage in the intestinal type of GC（36.7%） was much higher than that of the diffused type of GC（10.3%）.There was no significant relationship between the Her-2 protein expression and the patient’s age,gender,tumor location,and prognosis.Conclusion：Of the 198 GCs studied,Her-2 expression rate was 32%.Her-2 over expression was related to some biological behaviors related to gastric cancer.Her-2 expression in intestinal-type GC was significantly higher than that in the diffuse type of GC.Therefore,the patients with an intestinal type of GC would be the main population for Herceptin targeted therapy and might be the group that obtains benefi ts from the treatment.