显色原位杂交和免疫组织化学检测乳腺癌HER2/neu基因状况和蛋白表达的对照性研究

目的探讨显色原位杂交（CISH）在检测乳腺癌中HER2／neu基因扩增上的作用。方法挑选乳腺浸润性导管癌患者组织石蜡蜡块（回顾性255例,前瞻性271例）,进行免疫组织化学（IHC）、CISH检测。15例回顾性标本送往德国HERA检测中心进行FISH检测。结果（1）回顾性病例中IHC阳性3＋者CISH基因扩增率为91．6％（120／131）,IHC2＋者CISH基因扩增率为56．5％（39／69）,IHC与CISH检测结果符合率为81．2％（207／255）,两者明显相关（P〈0．01）。（2）前瞻性病例中IHC蛋白过表达率31．7％．CISH基因扩增率27．3％。IHC3＋者CISH基因扩增率为91．4％（53／58）,IHC2＋者CISH基因扩增率为46．4％（13／28）,IHC与CISH检测结果符合率为89．7％（243／271）,两者明显相关（P〈0．01）。（3）经德国检测中心荧光原位杂交（FISH）检测的15例中14例和CISH结果完全一致,1例检测失败,而CISH为无扩增。（4）CISH检测基因扩增与雌激素受体（ER）、孕激素受体（PR）表达明显负相关（P值均〈0．01）。结论CISH检测HER2基因扩增结果与IHC检测蛋白过表达及FISH结果高度一致,CISH是检测HER2基因扩增的一项新技术。

Comparision of HER2/neu oncogene detected by chromogenic in-situ hybridization and immunohistochemistry in breast cancer

Objective Through comparision of HER2/neu oncogene detected by chromogenic in situ hybridization(CISH)and immunohistochemistry(IHC)in breast cancer,to explore the effect of CISH on detecting gene amplification of HER2.Methods Selected formalin-fixed paraffin-embedded breast samples whose pathological types were infiltrating ductal carcinomas(255 retrospective samples,271 prospective samples),and these samples were detected by IHC and CISH.Results(1)In the retrospective study,CISH identified gene amplification in 91.6% of IHC score 3+tumors(120/131)and in 56.5% of IHC score 2+tumors(39/69),thus the concordant ratio between IHC and CISH was 81.2% (207/255).The two results showed significant correlation(P<0.01).(2)In the prospective study,the ratio of HER2 protein over expression detected by IHC was 31.7%,the ratio of HER2 gene amplification detected by CISH was 27.3%.CISH identified gene amplification in 91.4% of IHC score 3+tumors (53/58)and in 46.4% of IHC score 2+tumors(13/28),Concordant ratio between IHC and CISH was 89.7%(243/271).Two results showed significant correlation(P<0.01).(3)Paired CISH/FISH results were concordant in 14 of 15 cases.The remaining case was detected by FISH,but showed no HER2 gene amplification by CISH.(4)The gene amplification by CISH had a significantly reverse correlation with ER and PR expression(P<0.01).Conclusions The results of HER2 gene amplification detected by CISH have high concordance with the results detectd by IHC and FISH.CISH is a novel technique for detecting HER2 gene amplification.