HER2免疫组织化学结果为0的乳腺癌HER2 mRNA定量分析

Quantitative HER2 mRNA assay in breast cancer with HER2 immunohistochemistry 0

目的探讨HER2免疫组织化学(IHC)检测结果为0乳腺癌患者HER2 mRNA的表达特征,初步分析以HER2基因表达水平分层乳腺癌HER2超低表达和HER2无表达(IHC无染色)的可行性。方法收集北京协和医院2020年1月至2023年3月手术的甲醛固定石蜡包埋的浸润性乳腺癌组织标本41例,包括21例HER2 IHC 1+和20例HER2 IHC 0(HER2超低表达12例,HER2无表达8例)。采用数字PCR方法,以荧光FAM(HER2)/VIC(内参基因)比值计算HER2 mRNA水平。结果HER2 IHC 1+、HER2超低表达及HER2无表达的HER2 mRNA表达分别为0.30~1.78(平均0.90,中位0.82)、0.55~1.51(平均0.93,中位0.90)及0.22~0.78(平均0.41,中位0.36)。每组HER2 mRNA表达的平均值和中位值,HER2 IHC 1+和HER2超低表达之间差异无统计学意义(P=0.757);HER2 IHC 1+与HER2无表达及HER2超低表达与HER2无表达之间差异有统计学意义(分别P=0.002,P=0.001)。结论根据HER2 mRNA水平,HER2无表达与HER2弱表达(HER21+和HER2超低表达)属于两组不同的肿瘤;而HER21+和HER2超低表达可能是同一组肿瘤。有必要进一步验证以HER2 mRNA精细分层HER2弱表达的能力及确定阈值。

Objective To investigate HER2 mRNA expression in breast cancer with HER2 immunohistochemistry(IHC)0 and to analyze the feasibility of distinguishing between the tumor with HER2μltra-low expression and the one without expression of HER2(no staining by IHC)by HER2 mRNA level preliminarily.Methods HER2 mRNA was analyzed by reverse transcription digital PCR in 41 cases of formalin-fixed paraffin-embedded surgical tissue samples of invasive breast cancer obtained between January 2020 and March 2023 at Peking Union Medical College Hospital.The cohort included 21 HER2 IHC 1+and 20 IHC 0(12 ultra-low and 8 non-expression of HER2).HER2 mRNA expression level was quantitatively evaluated by the FAM(HER2)/VIC(reference gene)ratio.Results The expression of HER2 mRNA for the cases with 1+,ultra-low,and non-expression of HER2 by IHC was 0.30 to 1.78(average 0.90,median 0.82),0.55 to 1.51(average 0.93,median 0.90)and 0.22 to 0.78(average 0.41,median 0.36),respectively.For the mean and median HER2 mRNA levels,there was no significant difference between HER2 IHC 1+and HER2 ultra-low expression diseases(P=0.757).A remarkable difference in HER2 gene expression was found between the tumors with 1+and non-expression of HER2 by IHC(P=0.002).And,HER2 ultra-low cases contained statistically higher levels of HER2 mRNA compared with non-expression of HER2 subgroup by IHC(P=0.001).Conclusions Based on HER2 mRNA,HER2 non-expression and HER2 weak expression(including HER2 IHC 1+and ultra-low)belong to two different types of the tumor and the disease with HER2 IHC 1+and HER2 ultra-low expression may be the same.It is necessary to further test the performance of HER2 mRNA detection for stratifying the HER2 weak expression subgroup and to determine the threshold.