荧光原位杂交检测浸润性乳腺癌中人类表皮生长因子受体2基因临床应用的可行性研究

Clinical feasibility study of fluorescence in situ hybridization detection of Her-2 gene in breast cancer

目的比较免疫组织化学(IHC)及FISH2种方法检测浸润性乳腺癌中人类表皮生长因子受体2(Her-2)表达的差异性,同时探讨其临床病理联系,为FISH技术应用于Her-2的临床检测提供实验依据。方法采用IHC及FISH分别检测51例浸润性乳腺癌中Her-2蛋白表达及基因扩增,两种方法均严格按照美国临床肿瘤协会(ASCO)和美国病理家协会(CAP)联合制定的乳腺癌Her-2基因临床检测指南进行。结果 51例浸润性乳腺癌中,IHC染色-/+17例(33%)、++18例(35%)及+++16例(31%),FISH检测Her-2基因扩增阳性27例(53%),阴性24例(47%)。2种检测结果呈正相关(r=0.612,P<0.001)。同时实验表明IHC染色-/+的17例中Her-2基因扩增3例(18%),IHC++18例中Her-2基因扩增9例(50%),而IHC+++16例中Her-2基因扩增15例(94%),2种方法相比较差异有统计学意义(P<0.01)。本实验还显示Her-2基因的扩增与患者年龄、T分类、N分类、淋巴结转移及PR的表达状态等均无相关性,仅与ER的表达状态显著相关(P<0.01)。结论 IHC检测浸润性乳腺癌组织中Her-2的蛋白表达作为曲妥珠单抗药物选择的初筛手段,必要时还要联合FISH技术检测Her-2的基因扩增状态,方能准确指导临床选用曲妥珠单抗。

Objective To evaluate the differences of immunohistochemistry（IHC） and fluorescence in situ hybridization（FISH） in detecting the expression of Her-2 in the invasive breast cancer,and the relationship between Her-2 gene amplification and clinical pathology were also investigated.Methods The expression of Her-2 protein and the amplification of Her-2 gene in 51 invasive breast cancer tissues were detected by IHC and FISH,according with the Her-2 gene clinical testing guidelines in breast cancer that were developed jointly by the US.Society of Clinical Oncology（ASCO） and the College of American Pathologist（CAP）.Results The number of patients showed IHC（-/＋）,IHC（＋＋） and IHC（＋＋＋） was 17（33%）,18（35%） and 16（31%）,respectively.The ampli-fication of Her-2 gene existed in 27 cases（53%）,no amplification existed in 24 cases.There was positive correlation between the two results（r=0.612,P0.01）.FISH tests also showed that 3（18%） of 17 with IHC（-/＋）,9（50%） of 18 with IHC（＋＋）,and 15（94%） of 16 with IHC（＋＋＋） had Her-2 gene amplification.There were significant differences（P0.01） between the resnlts of IHC and FISH.This study also indicated that Her-2 gene amplification was only associated with ER expression status significantly（P〈0.01）.However,it was not associated with patient＇s age,T-classification,N-classi-fication,lymph node metastasis and the expression of progesterone receptor（PR） status.Conclusions The combination with FISH and IHC used to detect the expression of Her-2 status in invasive breast cancer is the best way which guide Herceptin screening,and the way is feasible and should be promoted in our country.