HER2 Score-Aware Virtual Immunohistochemistry via Non-Contrastive Multi-Task Translation

Background/Objectives: While human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) is pivotal for breast cancer management, its reliance on additional tissue processing beyond routine H&E staining remains a clinical burden. Although virtual staining offers a potential solution, current methods often fail to explicitly account for HER2 score-specific expression patterns. To address this gap, we developed a score-aware framework designed for the precise generation of virtual HER2 IHC images. Methods: We introduce the non-contrastive multi-task (NCMT) framework, which integrates negative-free patch alignment, style–content constraints, and auxiliary HER2 score supervision for high-fidelity H&E-to-IHC translation. For rigorous evaluation, the model was validated on the BCI dataset, utilizing an official split of 3896 training and 977 independent test images derived from 51 whole-slide images. Results: NCMT demonstrated superior virtual staining performance, achieving a Fréchet Inception Distance (FID) of 38.8, a Kernel Inception Distance (KID) of 5.6, and an average Perceptual Hash Value (PHV) of 0.439. In downstream HER2 scoring tasks, while virtual IHC images alone yielded an accuracy of 83.01%, the fusion of H&E and virtual IHC further elevated performance to 97.85% accuracy and a 98.23% F1 score. These findings suggest that our framework effectively preserves diagnostic features while providing complementary information to H&E-based morphological analysis. Conclusions: NCMT enables HER2 score-aware virtual IHC generation from H&E and can serve as a complementary tool for HER2 assessment in digital pathology.