Merlin Jean-Louis, Husson Marie, Sahki Nassim, Gilson Pauline, Massard Vincent, Harlé Alexandre, Leroux Agnès
Biopathology Department, Institut de Cancérologie de Lorraine-Alexis Vautrin, CNRS UMR7039 CRAN Université de Lorraine, 6 Avenue de Bourgogne, 54519 Vandœuvre-lès-Nancy, France.
Methodology Biostatistics Unit, Institut de Cancérologie de Lorraine-Alexis Vautrin, 54519 Vandoeuvre-lès-Nancy, France.
Biomedicines. 2023 Nov 28;11(12):3164. doi: 10.3390/biomedicines11123164.
Based on immunohistochemistry (IHC) and in situ hybridization (ISH), HER2-low breast cancers (BC) subtype-defined as IHC1+ or IHC2+/ISH- tumors-emerged and represent more than half of all BC. We evaluated the performance of NGS for integrated molecular characterization of HER2-low BC, including identification of actionable molecular targets, copy number variation (CNV), and microsatellite instability (MSI) analysis. Thirty-one BC specimens (11 HER2+, 10 HER2-, and 10 HER2-low) were routinely analyzed using IHC and ISH, and were selected and analyzed using NGS for gene mutations including , , , , , , and , CNV, and MSI. CNV values for the gene were significantly ( < 0.001) different between HER2+, and either HER2-low or HER2- tumors with mean values of 7.8 (SD = 6.8), 1.9 (SD = 0.3), and 2.0 (SD = 0.3), respectively. Using 3.25 as the cutoff value, 96.8% overall concordance of HER2 status was achieved between IHC and NGS compared to IHC and ISH. Using NGS, gene mutations and amplifications were detected in 68% (21/31) and 19% (6/31) of the cases, respectively. One case of MSI was detected in a HER2-negative and ISH unamplified case. Beside IHC, NGS allows the identification of HER2-low subtype simultaneously, with the detection of multiple actionable gene mutations being helpful for molecular board treatment selection.
基于免疫组织化学（IHC）和原位杂交（ISH），HER2低表达乳腺癌（BC）亚型被定义为IHC1 +或IHC2 + / ISH -肿瘤，其在所有乳腺癌中占比超过一半。我们评估了二代测序（NGS）对HER2低表达乳腺癌进行综合分子特征分析的性能，包括可操作分子靶点的鉴定、拷贝数变异（CNV）和微卫星不稳定性（MSI）分析。31例乳腺癌标本（11例HER2阳性、10例HER2阴性和10例HER2低表达）常规采用IHC和ISH进行分析，并选取这些标本用NGS分析包括、、、、、、和等基因的突变、CNV和MSI。HER2阳性与HER2低表达或HER2阴性肿瘤之间基因的CNV值存在显著差异（<0.001），其平均值分别为7.8（标准差=6.8）、1.9（标准差=0.3）和2.0（标准差=0.3）。以3.25作为临界值，与IHC和ISH相比，IHC和NGS之间HER2状态的总体一致性达到96.8%。使用NGS，分别在68%（21/31）和19%（6/31）的病例中检测到基因突变和扩增。在1例HER2阴性且ISH未扩增的病例中检测到1例MSI。除了IHC，NGS还能同时鉴定HER2低表达亚型，检测多个可操作基因突变有助于分子委员会治疗方案的选择。
