Zhan Haiying, Chan Nay Nwe Nyein, Khaimova Revekka, Aung Thazin N, Gaule Patricia, Robbins Charles J, Rimm David L
Department of Pathology, Yale School of Medicine, New Haven, CT, 06520, USA.
Department of Internal Medicine, Medical Oncology, Yale School of Medicine, New Haven, CT, 06520, USA.
Breast Cancer Res Treat. 2025 Jul 18. doi: 10.1007/s10549-025-07781-9.
Previous studies have demonstrated that ductal carcinoma in situ (DCIS) component often exhibits higher HER2 expression than the invasive component when assessed by immunohistochemistry, while some other studies showed concordant HER2 expression between these two components. In this study, we used our high-sensitivity HER2 (HS-HER2) quantitative immunofluorescence assay to compare HER2 expression in IDC and co-existing DCIS and correlate with clinicopathologic characteristics.
We included 36 IDC + DCIS cases from the Yale Pathology department. DCIS was classified according to the three-tier nuclear grading system: low (grade 1), intermediate (grade 2), and high (grade 3) nuclear grade. Invasive carcinoma was graded according to the modified Bloom-Richardson histologic grading system. Cases were divided into two groups: low to intermediate-grade DCIS (G1-2) with co-existing invasive carcinoma (n = 26) and high-grade DCIS (G3) with co-existing invasive carcinoma (n = 10). Separate regions of interest for IDC and DCIS were annotated by two board-certified pathologists. Serial sections of FFPE tumor specimens were used to accurately measure the HER2 protein expression by the HS-HER2 assay in attomole/mm unit and the acquisition by QuPath v.04 with the Qymia extension.
Low to intermediate-grade DCIS expressed higher HER2 levels (4295 ± 449 amol/mm) than co-existing invasive carcinoma (2880 ± 413 amol/mm). Similarly, high-grade DCIS expressed higher HER2 levels (4953 ± 700 amol/mm) than co-existing invasive carcinoma (3560 ± 688 amol/mm). Neither of these trends toward lower expression levels in the IDC were statistically significant. Additionally, no significant statistic difference was noted between low to intermediate-grade DCIS versus high-grade DCIS or between their corresponding co-existing invasive carcinomas in this cohort.
Using the HS-HER2 assay, our results demonstrated comparable HER2 expression levels in DCIS and paired invasive carcinoma regardless of histopathological grade or HER2 immunohistochemical score. These findings contributed to a more nuanced understanding of HER2 biology in early breast carcinogenesis and may inform future biomarker-driven therapeutic strategies.
既往研究表明，通过免疫组织化学评估时，导管原位癌（DCIS）成分的HER2表达通常高于浸润性成分，而其他一些研究则显示这两种成分的HER2表达一致。在本研究中，我们使用高灵敏度HER2（HS-HER2）定量免疫荧光检测方法，比较浸润性导管癌（IDC）和共存的DCIS中HER2的表达情况，并将其与临床病理特征相关联。
我们纳入了耶鲁病理科的36例IDC+DCIS病例。DCIS根据三级核分级系统进行分类：低（1级）、中（2级）和高（3级）核分级。浸润性癌根据改良的布鲁姆-理查森组织学分级系统进行分级。病例分为两组：共存浸润性癌的低至中级DCIS（G1-2）（n=26）和共存浸润性癌的高级DCIS（G3）（n=10）。两名获得委员会认证的病理学家对IDC和DCIS的不同感兴趣区域进行标注。使用福尔马林固定石蜡包埋（FFPE）肿瘤标本的连续切片，通过HS-HER2检测以阿托摩尔/毫米为单位准确测量HER2蛋白表达，并通过带有Qymia扩展程序的QuPath v.04进行采集。
低至中级DCIS的HER2水平（4295±449阿托摩尔/毫米）高于共存的浸润性癌（2880±413阿托摩尔/毫米）。同样，高级DCIS的HER2水平（4953±700阿托摩尔/毫米）高于共存的浸润性癌（3560±688阿托摩尔/毫米）。IDC中这些表达水平降低的趋势均无统计学意义。此外，在该队列中，低至中级DCIS与高级DCIS之间或其相应共存的浸润性癌之间未观察到显著的统计学差异。
使用HS-HER2检测方法，我们的结果表明，无论组织病理学分级或HER2免疫组织化学评分如何，DCIS和配对的浸润性癌中的HER2表达水平相当。这些发现有助于更细致地理解早期乳腺癌发生过程中的HER2生物学特性，并可能为未来基于生物标志物的治疗策略提供参考。
