Li Aidan C, Hammond Scott, Crosby Debra, Li Zaibo, Parwani Anil V
Department of Chemistry, Washington University in St. Louis, St. Louis, MO.
Department of Pathology, The Ohio State University Wexner Medical Center, Columbus, OH.
Clin Breast Cancer. 2025 Jan;25(1):38-45. doi: 10.1016/j.clbc.2024.10.004. Epub 2024 Oct 17.
HER2-targeted therapies have significantly improved outcomes for patients with HER2-positive breast cancer (BC), which represents 15% to 20% of all BC cases. HER2 status is assessed via immunohistochemistry (IHC) and/or in situ hybridization (ISH), dividing BCs into five groups (G1-G5).
In a study of 2,702 primary BC cases, comprising 12.7% G1, 0.2% G2, 2.8% G3, 8.5% G4, and 75.9% G5, we analyzed clinicopathologic features and HER2 protein expression digitally for each ISH group.
Notably, G5 cases had a higher proportion of lobular carcinoma (13.9%) compared to other groups. G3 cases showed the highest percentage of grade 3 tumors (56.9%), while G5 cases had the lowest (21.4%). Additionally, G5 cases had the highest rate of estrogen receptor (ER) positivity (84.6%), while G1-HC (high copy number) cases had the lowest (70.4%). Most G1-HC cases were HER2 IHC 3+ (76.1%), while most G5 cases were IHC 0/1+ (75.7%). IHC 2+ was most common in G1-LC (low copy number) and G3 cases (83.8% and 90.7%, respectively), with G4 cases predominantly IHC 2+ (56.3%) and IHC 1+ (30.1%). Discordant HER2 IHC and ISH results were observed in 12 cases (0.4%), including 7 G1-HC (2.3%), 4 G1-LC (10.8%), and 1 G5 case (0.1%). Digital quantification of HER2 IHC levels in all groups except G5 revealed that G1-HC tumors had the highest HER2 protein expression, followed by G3, with G4 showing the lowest.
These findings offer valuable insights into the clinicopathologic characteristics and future management for different HER2 ISH groups.
HER2靶向治疗显著改善了HER2阳性乳腺癌（BC）患者的预后，HER2阳性乳腺癌占所有乳腺癌病例的15%至20%。通过免疫组织化学（IHC）和/或原位杂交（ISH）评估HER2状态，将乳腺癌分为五组（G1 - G5）。
在一项对2702例原发性乳腺癌病例的研究中，包括12.7%的G1、0.2%的G2、2.8%的G3、8.5%的G4和75.9%的G5，我们对每个ISH组的临床病理特征和HER2蛋白表达进行了数字分析。
值得注意的是，与其他组相比，G5病例中小叶癌的比例更高（13.9%）。G3病例中3级肿瘤的百分比最高（56.9%），而G5病例中最低（21.4%）。此外，G5病例中雌激素受体（ER）阳性率最高（84.6%），而G1 - HC（高拷贝数）病例中最低（70.4%）。大多数G1 - HC病例为HER2 IHC 3 +（76.1%），而大多数G5病例为IHC 0/1 +（75.7%）。IHC 2 +在G1 - LC（低拷贝数）和G3病例中最常见（分别为83.8%和90.7%），G4病例主要为IHC 2 +（56.3%）和IHC 1 +（30.1%）。在12例（0.4%）病例中观察到HER2 IHC和ISH结果不一致，包括7例G1 - HC（2.3%）、4例G1 - LC（10.8%）和1例G5病例（0.1%）。除G5组外，所有组HER2 IHC水平的数字定量显示，G1 - HC肿瘤的HER2蛋白表达最高，其次是G3，G4最低。
这些发现为不同HER2 ISH组的临床病理特征和未来管理提供了有价值的见解。
