Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Breast Oncology, Peking University Cancer Hospital and Institute, Beijing, China.
Neoplasma. 2024 Aug;71(4):392-401. doi: 10.4149/neo_2024_240229N89.
Accurately distinguishing HER2-2+ tumors from HER2-0/1+ tumors via immunohistochemistry (IHC) is still very challenging. HER2 IHC 2+ is considered to indicate moderate expression and is easier to distinguish, with more reliable results in previous and current clinical practice. We focused on HER2-2+ patients and evaluated the switch in HER2 status between primary and paired recurrent disease patients to evaluate the discordance of HER2-2+ expression. We included patients who were HER2-2+ of primary or rebiopsy tumor samples, to evaluate the evolution of HER2-2+ expression. In the cohort with a total of 159 patients with HER2-2+ expression in either primary tumor or locoregional/distant metastasis samples, 44.0% had HER2-2+ in primary tumor and 88.8% in recurrent disease. Among patients with primary and recurrent HER2-2+ breast cancers, 18.5% and 15.2% of the patients, respectively, had HER2 gene amplification via ISH. The overall rate of discordance in HER2 IHC results was 67.1%. Among primary HER2-2+ patients, 74.6% were maintained in the HER2-2+ cohort at the recurrence. The discordance was mostly driven by patients switching from HER2-2+ to HER2-1+ (64.7%). Among HER2-2+ recurrent patients, discordance in the IHC results was mostly driven by switching from HER2-0 to HER2-2+ (47.1%). When HER2-low was added to the analysis, the overall rate of HER2 discordance was 40.4%. The proportion of patients with discordant HER2 expression was significantly greater among HR-positive patients than negative patients (44.1% vs. 21.7%, p=0.062). HER2 expression in primary and recurrent breast cancer samples was highly unstable. Discordance was more frequently observed in the HR-positive population.
通过免疫组织化学（IHC）准确地区分 HER2-2+肿瘤和 HER2-0/1+肿瘤仍然极具挑战性。HER2 IHC 2+被认为表示中度表达，并且更容易区分，在以前和当前的临床实践中具有更可靠的结果。我们专注于 HER2-2+患者，并评估原发性和配对复发性疾病患者之间的 HER2 状态变化，以评估 HER2-2+表达的不一致性。我们纳入了 HER2-2+的原发性或再活检肿瘤样本的患者，以评估 HER2-2+表达的演变。在总共 159 例原发性肿瘤或局部/远处转移样本中 HER2-2+表达的患者队列中，44.0%的患者在原发性肿瘤中 HER2-2+，88.8%的患者在复发性疾病中 HER2-2+。在原发性和复发性 HER2-2+乳腺癌患者中，分别有 18.5%和 15.2%的患者通过 ISH 存在 HER2 基因扩增。HER2 IHC 结果的总体不一致率为 67.1%。在原发性 HER2-2+患者中，74.6%的患者在复发时仍保留在 HER2-2+队列中。不一致主要是由从 HER2-2+转为 HER2-1+的患者驱动的（64.7%）。在 HER2-2+复发性患者中，IHC 结果的不一致主要是由从 HER2-0 转为 HER2-2+驱动的（47.1%）。当将 HER2-低加入分析时，HER2 不一致的总体率为 40.4%。在 HR 阳性患者中，HER2 表达不一致的患者比例明显高于 HR 阴性患者（44.1% vs. 21.7%，p=0.062）。原发性和复发性乳腺癌样本中的 HER2 表达高度不稳定。在 HR 阳性人群中更频繁地观察到不一致。
