乳腺癌HER2检测:单色与双色FISH评价系统的比较研究

HER-2 Testing in Breast Cancer:Comparison of Dual-Color and Single-Color FISH

目的旨在通过比较乳腺癌HER2检测单色与双色FISH评价系统的判读,提高HER2检测准确性、重复性以及改善对曲妥珠治疗反应的预测能力。方法按照2007年美国临床肿瘤学协会（ASCO）/美国病理医师学院（CAP）推荐的标准化操作,用免疫组化（Immunohistochemistry,IHC）和荧光原位杂交法（Fluorescence in Situ Hybridization,FISH）分别检测181例浸润性乳腺癌石蜡包埋标本中HER2基因的扩增及蛋白表达情况。比较IHC与FISH两种检测方法、双色FISH（Dual-Color FISH,D-FISH）与单色FISH（Single-Color FISH,S-FISH）两种评分系统的结果。结果本组IHC与D-FISH（P〈0.000 1）及S-FISH（P〈0.000 1）结果显著相关,其中IHC 0及3＋患者中,FISH与IHC结果的一致性达到了90%以上,而IHC 1＋~2＋组,结果吻合率低。D-FISH与S-FISH结果一致性为95%（χ2=138.38,P〈0.000 1）。两种评分系统对于HER2基因无扩增的判断基本一致,而对临界值的判定差异较大。结论 S-FISH评分系统对临界值的判断标准有待进一步商榷,对S-FISH诊断为临界值的病例应再行D-FISH检测,以便为临床治疗提供更精确地信息。

Objective To study the effect of dual-color（D-FISH） vs single-color FISH（S-FISH） scoring on the assignment of breast tumors to amplified or nonamplified HER2（human epidermal growth factor receptor 2,HER2） gene,and to improve the accuracy of HER2 testing and its utility as a predictive marker.Methods According to the American Society of Clinical Oncology/College of American Pathologists（ASCO/CAP） guideline about HER2 testing,181 cases of formalin-fixed and paraffin embedded invasive breast carcinomas samples were detected,and compared with results of immunohistochemistry（IHC） and fluorescence in situ hybridization（FISH） to analyzed HER2 expression and gene copy number.Results Analyzing concordance between IHC and FISH in HER-2 status and studying the results of D-FISH vs S-FISH scoring.Overall concordance in HER-2 status with immunohistochemical analysis was high not only for D-FISH（P0.000 1）,but also for S-FISH（P0.000 1）.Excellent concordance was found among groups scored IHC 0,3＋（more than 90%）.The discordant category was the group scored IHC 1＋ to 2＋.The D-FISH and the S-FISH results were concordant in 95% samples（χ2=138.38,P0.000 1）.To nonamplified group,the results from two kinds of scoring were so accordant,while for equivocal tumors,the most discordant judgments were found.Conclusion These results indicated that there was need further work to define equivocal result of single-color scoring.Cases interpreted as equivocal by S-FISH need to be repeated by D-FISH,and to gain accurate information for clinical therapy.