全自动免疫组织化学法检测肺腺癌组织中间变性淋巴瘤激酶融合基因表达情况

ALK fusion gene assessment by fully automatic immunohistochemistry in non-small cell lung cancer

目的 了解全自动免疫组织化学法检测肺腺癌组织中的间变性淋巴瘤激酶（ALK）蛋白表达的敏感度和特异度,探讨用免疫组织染色方法对肺腺癌患者进行ALK基因异常初筛的可能性.方法 收集2012年2月至12月共计404例肺腺癌手术标本,选肿瘤蜡块制备成组织芯片后,在全自动免疫组织化学染色仪上,采用Ventana抗ALK兔单克隆抗体（D5F3）和超敏检测系统进行染色,检测ALK蛋白表达情况,同时进行荧光原位杂交（FISH）法确认ALK融合基因阳性率.结果 404例肺腺癌标本中,375例ALK蛋白表达阴性,29例ALK蛋白表达阳性,阳性率为7.2％.29例ALK蛋白表达阳性的病例FISH检测均存在ALK融合基因,而375例ALK蛋白表达阴性的病例FISH检测均无ALK融合基因,灵敏度和特异度均为100％.结论 全自动免疫组织化学方法检测ALK蛋白可以作为肺腺癌患者抗ALK靶向治疗前一个经济、简单实用的筛选诊断方法,尚需临床上进一步验证.

Objective To evaluate the sensitivity and specificity of fully automated immunohistochemistry （IHC）,with comparison to FISH,in the detection of EML4-ALK rearrangement in lung adenocarcinoma （ADC） ; and the use of IHC as a pre-screening tool.Methods A total of 404 paraffin-embedded NSCLC samples from surgical resections were tested by IHC with Ventana anti-ALK rabbit monoclonal antibody （D5F3） and ultrasensitive detection kit.ALK rearrangement was further confirmed by FISH.Results Twenty-nine of 404 lung ADCs （7.2％） were positive for ALK by IHC.ALK positive tumor cells demonstrated strong and diffused granular cytoplasmic staining.All the ALK IHC-positive cases were confirmed to harbor ALK rearrangement by FISH.None of the ALK IHC-negative cases was FISH-positive.Conclusions IHC can effectively detect ALK rearrangement in lung cancer.It may provide a reliable and cost-effective diagnostic approach in routine pathologic laboratories for the identification of suitable candidates for ALK-targeted therapy.