Liu Yuanyuan, Wu Shafei, Shi Xiaohua, Mao Feng, Zeng Xuan
Molecular Pathology Research Center, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Department of Breast Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Front Oncol. 2020 Jun 19;10:985. doi: 10.3389/fonc.2020.00985. eCollection 2020.
For breast cancer, accurately illustrating HER2 characteristics is a critical precondition for evaluating the prognosis and predicting the efficacy of anti-HER2 therapy. Our purpose was to expose HER2 mRNA expression through an hybridization assay (RNAscope), to aid the identification of HER2 status in breast cancers with a previously controversial classification for patients suffering from a HER2 IHC2+ and HER2/CEP17 ≥2.0 and a <4.0 mean HER2 gene copy number/cell (entitled FISH group 2 by update 2018 HER2 testing guideline). A total of 8,983 cases of breast cancer with a known HER2 status detected by initial IHC, and a necessary reflex FISH assay for those with IHC2+, were retrospectively analyzed. Then, 41 cases of HER2 IHC2+ in the FISH group 2 were collected and a RNAscope was performed. The incidence of breast cancers with IHC2+ and in the FISH group 2 was 0.46% (41/8,983) in our single-institutional study cohort. In most of the cases (27/41, 65.9%), low levels of HER2 mRNA expression (score 1 and 2 by RNAscope) were demonstrated. Only one case (1/41, 2.4%) of high-level HER2 mRNA expression (score 4 by RNAscope), harboring a FISH HER2/CEP17 ratio of 2.06 and an average HER2 copy number of 3.70, was revealed. One case with the highest FISH HER2/CEP17 ratio of 3.90, showed the lowest level of HER2 mRNA expression (score 1 by RNAscope). Two cases with the same highest average HER2 signals/cell (3.95) by FISH possessed score 3 and score 2 with RNAscope, respectively. No cases with a score of 0 by RNAscope occurred in our sample. In the majority of cases (35/41, 85.4%), hypodisomy of chromosome 17 (average CEP17 signals/cell ≤1.75) was observed. There was no significant relationship between the mRNA expression and FISH results (average HER2 signals/cell, average CEP17 copy number, or HER2/CEP17 ratio) and clinicopathological features (ER and PR statuses, Ki 67 index, tumor size, and lymph node metastasis) in our population. HER2 mRNA overexpression was not a feature in our group of patients. Based on our data, breast cancers with HER2 IHC2+ and in FISH group 2 support a categorization of HER2 negative.
对于乳腺癌，准确阐明HER2特征是评估预后和预测抗HER2治疗疗效的关键前提。我们的目的是通过杂交检测法（RNAscope）检测HER2 mRNA表达，以辅助确定HER2免疫组化（IHC）2+且HER2/着丝粒蛋白17（CEP17）≥2.0且平均HER2基因拷贝数/细胞<4.0（根据2018年HER2检测指南更新版属于FISH 2组）的乳腺癌患者的HER2状态。对8983例经初始IHC检测已知HER2状态且对IHC2+患者进行必要的FISH检测的乳腺癌病例进行回顾性分析。然后，收集FISH 2组中的41例HER2 IHC2+病例并进行RNAscope检测。在我们单中心研究队列中，IHC2+且属于FISH 2组的乳腺癌发生率为0.46%（41/8983）。在大多数病例（27/41，65.9%）中，HER2 mRNA表达水平较低（RNAscope评分为1和2）。仅发现1例（1/41，2.4%）HER2 mRNA高表达（RNAscope评分为4），其FISH检测的HER2/CEP17比值为2.06，平均HER2拷贝数为3.70。1例FISH检测HER2/CEP17比值最高为3.90的病例，HER2 mRNA表达水平最低（RNAscope评分为1）。2例FISH检测平均HER2信号/细胞相同最高值（3.95）的病例，RNAscope评分分别为3和2。我们的样本中未出现RNAscope评分为0的病例。在大多数病例（35/41，85.4%）中，观察到17号染色体亚二倍体（平均CEP17信号/细胞≤1.75）。在我们的研究人群中，mRNA表达与FISH结果（平均HER2信号/细胞、平均CEP17拷贝数或HER2/CEP17比值）以及临床病理特征（雌激素受体和孕激素受体状态、Ki 67指数、肿瘤大小和淋巴结转移）之间无显著相关性。我们的患者组中不存在HER2 mRNA过表达特征。根据我们的数据，HER2 IHC2+且属于FISH 2组的乳腺癌支持HER2阴性分类。
