新旧两版指南对浸润性乳腺癌HER-2基因扩增的判读影响

Interpretation of HER-2 gene amplification in invasive breast cancer based on old and new guidelines

目的探讨2014版与2019版《乳腺癌HER-2检测指南》对浸润性乳腺癌HER-2基因扩增的判读影响。方法收集698例浸润性乳腺癌石蜡标本,采用免疫组化(immunohistochemistry,IHC)法和荧光原位杂交(fluorescence in situ hybridization,FISH)法对HER-2蛋白表达和基因扩增进行检测,并用2014和2019版指南分别对检测结果进行判读。结果根据2014版指南FISH判读法检测HER-2基因扩增的阳性检出率为40.7%(284/698),阴性检出率为52.1%(364/698),不确定为7.2%(50/698)。根据2019版指南FISH判读法检测HER-2基因扩增的阳性检出率为40.0%(279/698),阴性检出率为60.0%(419/698)。两版指南中IHC与FISH法检测HER-2蛋白表达与基因扩增的总一致率分别为54.7%、55.7%;两版检测结果具有一致性(Kappa=0.277,P<0.001;Kappa=0.251,P<0.001),且均呈正相关(r=0.608,P<0.001;r=0.641,P<0.001)。结论2019版指南取消FISH法检测HER-2基因扩增的不确定结果,使其阴性率有所增加,更加明确了HER-2基因状态,为临床靶向治疗提供参考。

Purpose To investigate the influence of the 2014 and 2019 versions of the Guideline for HER-2 Detection in Breast Cancer on the interpretation of invasive breast cancer HER-2 gene amplification.Methods Paraffin-embedded specimens were collected from 698 patients with invasive breast cancer.Immunohistochemistry(IHC)and fluorescence in situ hybridization(FISH)were used to detect HER-2 protein expression and gene amplification,and the test results were interpreted with the 2014 and 2019 version guidelines respectively.Results According to the 2014 guidelines,the positive rate of HER-2 gene amplification by FISH method was 40.7%(284/698),the negative rate was 52.1%(364/698),and the suspicious rate was 7.2%(50/698).According to the 2019 guidelines,the positive rate of HER-2 gene amplification by FISH method was 40.0%(279/698)and the negative rate was 60.0%(419/698).The coincidence rate of HER-2 protein expression and gene amplification detected by IHC and FISH in the two versions of guidelines were 54.7%and 55.7%respectively,and the results were consistent(Kappa=0.277,P<0.001,Kappa=0.251,P<0.001),and positively correlated(r=0.608,P=0.000,r=0.641,P<0.001).Conclusion The uncertain results of HER-2 gene amplification detected by FISH have been cancelled in guidance of the 2019 edition,which increases the negative rate,more clearly defines the HER-2 gene status,and provides a more perfect basis for targeted therapy in clinical practice.