Immunohistochemistry, next generation sequencing (NGS), and whole exome sequencing concordance in HER2 testing in uterine serous carcinoma: a retrospective analysis

IF 4.1 2区医学 Q1 OBSTETRICS & GYNECOLOGY

Gynecologic oncology Pub Date : 2025-10-14 DOI:10.1016/j.ygyno.2025.09.017

Victoria M. Ettorre , Stefania Bellone , Natalia Buza , Pei Hui , Tobias Max Philipp Hartwich , Cem Demirkiran , Michelle Greenman , Namrata Sethi , Luca Palmieri , Alessandro D. Santin

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引用次数: 0

Abstract

Background

HER2-targeted treatments are an important therapeutic option for a subset of uterine serous carcinoma (USC) patients. We evaluated the concordance of routine immunohistochemistry (IHC) testing and fluorescence in situ hybridization (FISH) for HER2 expression versus next generation sequencing (NGS) by a commercial platform (Foundation Medicine), and comprehensive whole exome sequencing (WES).

Methods

Two groups of USC patients with IHC and FISH results for HER2 were compared for concordance with matched NGS data (152 USC patients) and WES (76 USC patients) performed at the Yale Center for Genome Analysis (YCGA). Clinical HER2 positivity was defined as 3+ IHC staining or 2+ IHC staining with reflex gene amplification utilizing fluorescent-in-situ-hybridization (FISH). NGS HER2 positivity was defined as ERBB2 amplifications identified in the NGS/WES report.

Results

In the IHC/NGS group, the overall correlation was 81 % (p < 0.001), which improved to 85 % (p < 0.001) when IHC/FISH and NGS were performed on the same pathology tissue block of a particular specimen. In the IHC/WES group, the overall correlation was similar at 82 % (p < 0.001). NGS captured 1 additional patient missed by IHC/FISH, while WES captured 11 additional patients not identified by IHC/FISH.

Conclusions

The correlation of HER2 IHC/FISH with NGS and WES ranges between 80 and 85 %, with improvement in correlation when testing is performed on the same tissue block. WES may be superior to commercially available NGS platforms in the detection/identification of HER2 treatment-eligible patients. While highly correlated, these results confirm that IHC should not be abandoned in the evaluation of patients eligible for HER2-targeted therapy.

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免疫组织化学、下一代测序（NGS）和全外显子组测序在子宫浆液性癌HER2检测中的一致性：回顾性分析。

背景：her2靶向治疗是子宫浆液性癌（USC）患者的重要治疗选择。我们评估了常规免疫组织化学（IHC）检测和荧光原位杂交（FISH）检测HER2表达与商业平台（基础医学）的下一代测序（NGS）和综合全外显子组测序（WES）的一致性。方法：将两组USC患者的IHC和FISH结果与耶鲁大学基因组分析中心（YCGA）进行的匹配NGS数据（152例USC患者）和WES数据（76例USC患者）的一致性进行比较。临床HER2阳性定义为3+ IHC染色或2+ IHC染色，利用荧光原位杂交（FISH）反射基因扩增。NGS HER2阳性定义为NGS/WES报告中确定的ERBB2扩增。结果：在IHC/NGS组中，HER2 IHC/FISH与NGS和WES的相关性在80 - 85%之间，当在同一组织块上进行检测时，相关性有所提高。在检测/鉴定HER2治疗合格患者方面，WES可能优于市售的NGS平台。虽然高度相关，但这些结果证实，在评估符合her2靶向治疗条件的患者时，不应放弃免疫组化。

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

Gynecologic oncology 医学-妇产科学

CiteScore

8.60

自引率

6.40%

发文量

1062

审稿时长

37 days

期刊介绍： Gynecologic Oncology, an international journal, is devoted to the publication of clinical and investigative articles that concern tumors of the female reproductive tract. Investigations relating to the etiology, diagnosis, and treatment of female cancers, as well as research from any of the disciplines related to this field of interest, are published. Research Areas Include: • Cell and molecular biology • Chemotherapy • Cytology • Endocrinology • Epidemiology • Genetics • Gynecologic surgery • Immunology • Pathology • Radiotherapy