HER2 amplification status in breast cancer: a comparison between immunohistochemical staining and fluorescence in situ hybridisation using manual and automated quantitative image analysis scoring techniques.

J Clin Pathol

Department of Cytogenetics, Sheffield Genetics Services, Sheffield Children's NHS Trust, Western Bank, Sheffield S10 2TH, UK.

Published: July 2005

Aims: To compare the results of breast cancer sections with HercepTesttrade mark immunohistochemistry (IHC) scores ranging from 0 to 3+ with fluorescence in situ hybridisation (FISH) for HER2 amplification. The HER2 digital scoring application of the Micrometastasis Detection System (MDS) was used, together with manual scoring of FISH and HercepTest, to determine whether this system provides an accurate alternative.

Methods: Paraffin wax embedded sections were stained using HercepTest and analysed by eye and automated quantitative image analysis. FISH was performed using the PathVysion fluorescent probe and scored by eye and automated quantitative image analysis using MDS.

Results: Of 114 cases, 26% were amplified by FISH, whereas only 18% scored 3+; 32% of IHC 2+ cases were amplified by FISH, and one showed borderline amplification. Six percent of IHC negative cases (0 or 1+) were amplified by FISH, and one showed borderline amplification. Of IHC 3+ cases, 10% were non-amplified by FISH. Classification discrepancies were seen in 18% of HercepTest cases scored by eye and using the MDS system. MDS was consistent with visual FISH scoring and correctly differentiated most ambiguous visual IHC scores.

Conclusions: FISH provides a more accurate and consistent scoring system for determining HER2 amplification than HercepTest. The MDS system provides a reliable, consistent alternative to visual IHC and FISH scoring. IHC is still a valuable technique to aid in identification of isolated or heterogeneous tumour populations for subsequent FISH analysis, and a combined FISH and HercepTest approach to all breast cancer cases may be the most efficient strategy.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770709PMC
http://dx.doi.org/10.1136/jcp.2004.023424DOI Listing

Publication Analysis

Top Keywords

her2 amplification
12
breast cancer
12
automated quantitative
12
quantitative image
12
image analysis
12
fish
12
amplified fish
12
fluorescence situ
8
situ hybridisation
8
system mds
8

Similar Publications

Impacts of genomic alterations on the efficacy of HER2-targeted antibody-drug conjugates in patients with metastatic breast cancer.

J Transl Med

January 2025

State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, No.651 Dongfeng East Road, Guangzhou, 510060, People's Republic of China.

Background: HER2-targeted antibody-drug conjugates (ADCs) have revolutionized the treatment landscape of metastatic breast cancer. However, the efficacy of these therapies may be compromised by genomic alterations. Hence, this study aims to identify factors predicting sensitivity to HER2 ADC in metastatic breast cancer.

View Article and Find Full Text PDF

Triple-negative breast cancers (TNBCs) are invasive carcinomas that lack ER and PR expression and also lack amplification or overexpression of HER2. Triple-negative breast cancers are histopathologically diverse, with the majority classified as invasive breast carcinomas of no special type with a basal-like profile. Triple-negative breast cancer is the most aggressive molecular subtype of invasive breast carcinoma, with the highest rates of stage-matched mortality and regional recurrence.

View Article and Find Full Text PDF

Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.

View Article and Find Full Text PDF

Purpose: Breast cancer subtypes are delineated by human epidermal growth factor receptor 2 (HER2) expression, pivotal in treatment selection. HER2-positive tumors typically respond to targeted therapies, whereas HER2-negative tumors lack HER2 overexpression. However, a subset exhibits low HER2 expression without amplification, termed HER2 low breast cancer.

View Article and Find Full Text PDF

The most common histological subtypes of endometrial cancer consist of endometrioid and uterine serous carcinoma, with the latter being more aggressive and accompanied by poor prognosis. Human epidermal growth factor receptor 2 (HER2) is a transmembrane tyrosine kinase receptor associated with cell proliferation, differentiation, and survival. HER2 positivity can be diagnosed in many solid tumors.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!