Quantitative assessment of HER2 expression in invasive ductal carcinoma and co-existing DCIS.

IF 3 3区医学 Q2 ONCOLOGY

Breast Cancer Research and Treatment Pub Date : 2025-09-01 Epub Date: 2025-07-18 DOI:10.1007/s10549-025-07781-9

Haiying Zhan, Nay Nwe Nyein Chan, Revekka Khaimova, Thazin N Aung, Patricia Gaule, Charles J Robbins, David L Rimm

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引用次数: 0

Abstract

Purpose: 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.

Methods: 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/mm² unit and the acquisition by QuPath v.04 with the Qymia extension.

Results: Low to intermediate-grade DCIS expressed higher HER2 levels (4295 ± 449 amol/mm²) than co-existing invasive carcinoma (2880 ± 413 amol/mm²). Similarly, high-grade DCIS expressed higher HER2 levels (4953 ± 700 amol/mm²) than co-existing invasive carcinoma (3560 ± 688 amol/mm²). 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.

Conclusion: 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.

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浸润性导管癌及合并DCIS中HER2表达的定量分析。

目的：以往的研究表明，在免疫组化评估中，导管原位癌（ductal carcinoma in situ， DCIS）成分的HER2表达往往高于浸润性成分，而其他一些研究显示这两种成分的HER2表达一致。在本研究中，我们使用高灵敏度HER2 （HS-HER2）定量免疫荧光法比较了HER2在IDC和共存DCIS中的表达，并与临床病理特征进行了相关性分析。方法：选取耶鲁大学病理科36例IDC + DCIS病例。DCIS按照三级核分级系统进行分类：低（1级）、中（2级）、高（3级）核分级。浸润性癌根据改良的Bloom-Richardson组织学分级系统进行分级。将病例分为低至中级别DCIS （G1-2）合并浸润性癌（n = 26）和高级别DCIS （G3）合并浸润性癌（n = 10）两组。两名委员会认证的病理学家对IDC和DCIS的不同兴趣区域进行了注释。利用连续切片的FFPE肿瘤标本，通过以原子摩尔/mm2为单位的HS-HER2检测和Qymia扩展的QuPath v.04获取，准确测量HER2蛋白的表达。结果：低至中级别DCIS的HER2表达水平（4295±449 amol/mm2）高于共存的浸润性癌（2880±413 amol/mm2）。同样，高级别DCIS表达的HER2水平（4953±700 amol/mm2）高于共存的浸润性癌（3560±688 amol/mm2）。在IDC中，这两种低表达水平的趋势均无统计学意义。此外，在该队列中，低、中级别DCIS与高级别DCIS之间以及相应的共存浸润性癌之间没有显著的统计学差异。结论：使用HS-HER2检测，我们的结果显示，无论组织病理分级或HER2免疫组织化学评分如何，DCIS和配对的浸润性癌中HER2表达水平相当。这些发现有助于更细致地了解早期乳腺癌发生中的HER2生物学，并可能为未来的生物标志物驱动的治疗策略提供信息。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast Cancer Research and Treatment 医学-肿瘤学

CiteScore

6.80

自引率

2.60%

发文量

342

审稿时长

1 months

期刊介绍： Breast Cancer Research and Treatment provides the surgeon, radiotherapist, medical oncologist, endocrinologist, epidemiologist, immunologist or cell biologist investigating problems in breast cancer a single forum for communication. The journal creates a "market place" for breast cancer topics which cuts across all the usual lines of disciplines, providing a site for presenting pertinent investigations, and for discussing critical questions relevant to the entire field. It seeks to develop a new focus and new perspectives for all those concerned with breast cancer.