Novel approach to HER2 quantification using phosphor-integrated dots in human breast invasive cancer microarray

Area of Science:

• Oncology
• Pathology
• Biotechnology

Background:

• Accurate HER2 (Human Epidermal growth factor Receptor 2) expression assessment is crucial for selecting breast cancer patients for anti-HER2 targeted therapies.
• The development of new HER2-targeted drugs for low HER2 expression breast cancer necessitates a comprehensive understanding of the entire spectrum of HER2 expression.
• Current immunohistochemistry (IHC) methods may require enhanced quantitative analysis for precise HER2 evaluation, especially in borderline cases.

Purpose of the Study:

• To quantitatively assess HER2 expression in invasive breast cancer using a novel approach combining phosphor-integrated dot (PID) immunostaining and whole slide imaging (WSI).
• To evaluate the correlation between PID-based quantitative HER2 assessment and traditional ASCO/CAP guideline-based IHC scoring.
• To determine the utility of digital image analysis for stratifying HER2 IHC and classifying low HER2 expression.

Main Methods:

• A 170-core tissue microarray of invasive breast cancer was utilized.
• HER2 expression was assessed using two methods: standard immunohistochemistry (IHC) scored by pathologists and quantitative analysis of PID-stained samples.
• Whole slide imaging (WSI) was employed for digital analysis of PID immunostaining.

Main Results:

• Phosphor-integrated dot (PID) immunostaining allowed for numerical classification of HER2 expression into scores 3+, 2+, 1+, and 0.
• The HER2 values quantified by PID showed a strong correlation with the 3,3'-diaminobenzidine (DAB) IHC scores determined by pathologists (R² = 0.93).
• PID analysis revealed that cases with low HER2 expression (DAB IHC score 0) were sometimes classified as PID IHC score 1+, suggesting improved sensitivity for detecting low expression.

Conclusions:

• Digital image analysis combining PID immunostaining and WSI provides a robust quantitative method for assessing HER2 expression in breast cancer.
• This approach can effectively stratify HER2 IHC results and offers potential for more accurate classification of low HER2 expression.
• The findings support the use of PID and WSI as valuable tools for enhancing HER2 assessment in clinical practice, particularly with the emergence of new targeted therapies.