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

## TL;DR

This study introduces a new method using phosphor-integrated dots to accurately measure HER2 expression in breast cancer, which could improve patient selection for therapy.

## Contribution

The novel use of phosphor-integrated dots combined with whole slide imaging provides a quantitative approach to HER2 expression assessment.

## Key findings

- PID staining strongly correlates with traditional IHC scores (R2 = 0.93).
- PID can numerically classify HER2 expression into distinct categories.
- Low HER2 expression cases are often misclassified as IHC score 0.

## Abstract

HER2 expression in breast cancer is evaluated to select patients for anti-HER2 therapy. With the advent of newly approved HER2-targeted drugs for low HER2 expression breast cancer, more solid evidence on the whole spectrum of HER2 expression is needed. In this study, we quantitatively assessed HER2 expression from the whole core by combining high-intensity phosphor-integrated dot (PID) immunostaining and whole slide imaging (WSI) analysis. Two types of staining were performed using a 170-core tissue microarray of invasive breast cancer. First, HER2 was stained by immunohistochemistry (IHC), and IHC scores were determined by two practicing pathologists according to the ASCO/CAP HER2 guideline. Second, HER2 was stained with PID, and tentative PID scores were determined by quantitative analysis. The results show that PID can numerically classify HER2 expression status into scores 3+, 2+, 1+, and 0. The HER2 value quantified by PID strongly correlated with the 3, 3’-diaminobenzidine (DAB) IHC score determined by pathologists (R2 = 0.93). PID IHC score 1+ cases included both DAB IHC score 1+ and 0 cases, and low HER2 expression cases appeared to be often evaluated as DAB IHC score 0. Therefore, digital image analysis by PID and WSI can help stratify HER2 IHC. It may also help classify low HER2 expression.