Department of Histopathology, School of Medicine, the University of Nottingham and Nottingham University, Hospitals NHS Trust, Nottingham, UK.
Department of Pathology, Faculty of Medicine, Menoufia University, Menoufia, Egypt.
Histopathology. 2022 Dec;81(6):770-785. doi: 10.1111/his.14780. Epub 2022 Sep 12.
Emerging evidence indicates that breast cancer (BC) patients whose tumours express HER2 protein without HER2 gene amplification (HER2-low), can benefit from antibody-drug conjugates (ADC). However, the current definition of HER2-low BC remains incomplete with low rates of concordance. This study aims to refine HER2-low definition with emphasis on distinguishing HER2 score 0 from score 1+ to identify patients who are eligible for ADC.
A BC cohort (n = 363) with HER2 IHC scores 0, 1+ and 2+ (without HER2 gene amplification) and available HER2 mRNA was included. HER2 staining intensity, pattern and subcellular localisation were reassessed. Artificial neural network analysis was applied to cluster the cohort and to distinguish HER2 score 0 from 1+. Reproducibility and reliability of the refined criteria were tested.
HER2 IHC score 1+ was refined as membranous staining in invasive cells as either: (1) faint intensity in ≥ 20% of cells regardless the circumferential completeness, (2) weak complete staining in ≤ 10%, (3) weak incomplete staining in > 10% and (4) moderate incomplete staining in ≤ 10%. Based on this, 63% of the HER2-negative cases were reclassified as positive (HER2-low). The refined score showed perfect observer agreement compared to the moderate agreement in the original clinical scores. Similar results were generated when the refined score was applied on the independent BC cohorts. A proposal to refine the definition of other HER2 classes is presented.
This study refined the definition of HER2-low BC based on correlation with HER2 mRNA and distinguished between HER2 IHC score 1+ and score 0 tumours.
新出现的证据表明，表达 HER2 蛋白但无 HER2 基因扩增的乳腺癌（BC）患者（HER2-低）可从抗体药物偶联物（ADC）中获益。然而，目前的 HER2-低 BC 定义并不完整，一致性率较低。本研究旨在通过强调区分 HER2 评分 0 与评分 1+，来完善 HER2-低的定义，以确定有资格接受 ADC 治疗的患者。
本研究纳入了 HER2 IHC 评分 0、1+和 2+（无 HER2 基因扩增）且有 HER2 mRNA 结果的 BC 队列（n=363）。重新评估了 HER2 染色强度、模式和亚细胞定位。应用人工神经网络分析对队列进行聚类，以区分 HER2 评分 0 与 1+。检验了改良标准的重现性和可靠性。
HER2 IHC 评分 1+被改良为浸润性细胞的膜染色，其特征为：（1）无论环状完整性如何，细胞中≥20%的染色强度微弱，（2）≤10%的弱完全染色，（3）>10%的弱不完整染色和（4）≤10%的中度不完整染色。在此基础上，63%的 HER2 阴性病例被重新分类为阳性（HER2-低）。与原始临床评分中度一致性相比，改良评分显示出完美的观察者一致性。当将改良评分应用于独立的 BC 队列时，也得到了类似的结果。还提出了改良其他 HER2 类别的定义的建议。
本研究基于与 HER2 mRNA 的相关性，对 HER2-低 BC 的定义进行了改良，并区分了 HER2 IHC 评分 1+和评分 0 肿瘤。
