Automated HER2 scoring with uncertainty quantification using lensfree holography and deep learning

TL;DR

This paper introduces a portable, cost-effective lensfree holography system combined with deep learning and uncertainty quantification for accurate, high-throughput HER2 scoring in breast cancer tissue, suitable for resource-limited settings.

Contribution

It presents a novel lensfree holography platform integrated with deep learning and Bayesian uncertainty quantification for automated HER2 scoring, improving accessibility and reliability.

Findings

Achieved 84.9% accuracy for 4-class HER2 classification.

Achieved 94.8% accuracy for binary HER2 scoring.

Supported high-throughput analysis at ~84 mm^2 per minute.

Abstract

Accurate assessment of human epidermal growth factor receptor 2 (HER2) expression is critical for breast cancer diagnosis, prognosis, and therapy selection; yet, most existing digital HER2 scoring methods rely on bulky and expensive optical systems. Here, we present a compact and cost-effective lensfree holography platform integrated with deep learning for automated HER2 scoring of immunohistochemically stained breast tissue sections. The system captures lensfree diffraction patterns of stained HER2 tissue sections under RGB laser illumination and acquires complex field information over a sample area of ~1,250 mm^2 at an effective throughput of ~84 mm^2 per minute. To enhance diagnostic reliability, we incorporated an uncertainty quantification strategy based on Bayesian Monte Carlo dropout, which provides autonomous uncertainty estimates for each prediction and supports reliable, robust HER2 scoring, with an overall correction rate of 30.4%. Using a blinded test set of 412 unique tissue samples, our approach achieved a testing accuracy of 84.9% for 4-class (0, 1+, 2+, 3+) HER2 classification and 94.8% for binary (0/1+ vs. 2+/3+) HER2 scoring with uncertainty quantification. Overall, this lensfree holography approach provides a practical pathway toward portable, high-throughput, and cost-effective HER2 scoring, particularly suited for resource-limited settings, where traditional digital pathology infrastructure is unavailable.