Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mol Cancer Ther. 2023 Aug 1;22(8):976-984. doi: 10.1158/1535-7163.MCT-22-0630.
We sought to assess discordance of HER2 status in patients with HER2-amplified/expressing solid tumors who underwent reevaluation of HER2 status. Patients with metastatic solid tumors and HER2 expression by IHC or amplification by FISH/next-generation sequencing on local testing underwent central HER2 IHC/FISH testing with either archival or fresh biopsies and were evaluated for discordance in HER2 status. 70 patients (12 cancer types) underwent central HER2 reevaluation, including 57 (81.4%) with a new biopsy. In 30 patients with HER2 3+ on local IHC, 21 (70.0%) were 3+, 5 (16.7%) were 2+, 2 (6.7%) were 1+, and 2 (6.7%) had 0 HER2 expression on central IHC. In 15 patients whose cancers were 2+ on local IHC, 2 (13.3%) were 3+, 5 (33.3%) were 2+, 7 (46.7%) were 1+, and 1 (6.7%) had 0 HER2 expression on central IHC. HER2 discordance was seen in 16 of 52 (30.8%) of patients with HER2 overexpression/amplification who underwent a new image-guided biopsy. Discordance was observed in 10 (33.3%) of 30 patients who received intervening HER2-targeted therapy and in 6 (23.8%) of 22 patients who did not. In the 8 patients who had central HER2 assessment from the same archival block used for local testing, none were discordant. Discordance of HER2 status is common in patients with tumors previously identified as HER2-expressing, especially in patients with HER2 2+ tumors. Repeat biomarker evaluation may have value when considering HER2-targeted therapies.
我们旨在评估 HER2 扩增/表达的实体瘤患者重新评估 HER2 状态时的 HER2 状态不一致性。局部检测 IHC 或 FISH/下一代测序检测到 HER2 表达或扩增的转移性实体瘤患者接受了中央 HER2 IHC/FISH 检测，使用存档或新鲜活检，并评估了 HER2 状态的不一致性。70 名患者（12 种癌症类型）接受了中央 HER2 重新评估，其中 57 名（81.4%）患者进行了新的活检。在 30 名局部 IHC 为 3+的 HER2 患者中，21 名（70.0%）为 3+，5 名（16.7%）为 2+，2 名（6.7%）为 1+，2 名（6.7%）为 0 表达。在 15 名局部 IHC 为 2+的癌症患者中，2 名（13.3%）为 3+，5 名（33.3%）为 2+，7 名（46.7%）为 1+，1 名（6.7%）为 0 表达。在 52 名接受新的图像引导活检的 HER2 过表达/扩增患者中，有 16 名（30.8%）出现 HER2 不一致。在 30 名接受介入性 HER2 靶向治疗的患者中观察到不一致性，在 22 名未接受介入性 HER2 靶向治疗的患者中观察到 6 名（23.8%）出现不一致性。在 8 名从用于局部检测的同一存档块进行中央 HER2 评估的患者中，均无不一致性。在先前被确定为 HER2 表达的肿瘤患者中，HER2 状态不一致很常见，尤其是在 HER2 2+肿瘤患者中。在考虑 HER2 靶向治疗时，重复生物标志物评估可能具有价值。
