Cross-Stain Contrastive Learning for Paired Immunohistochemistry and Histopathology Slide Representation Learning

Authors

Yizhi Zhang, Lei Fan, Zhulin Tao, Donglin Di, Yang Song, Sidong Liu, Cong Cong

Categories

Abstract

Universal, transferable whole-slide image (WSI) representations are central to computational pathology. Incorporating multiple markers (e.g., immunohistochemistry, IHC) alongside H&E enriches H&E-based features with diverse, biologically meaningful information. However, progress is limited by the scarcity of well-aligned multi-stain datasets. Inter-stain misalignment shifts corresponding tissue across slides, hindering consistent patch-level features and degrading slide-level embeddings. To address this, we curated a slide-level aligned, five-stain dataset (H&E, HER2, KI67, ER, PGR) to enable paired H&E-IHC learning and robust cross-stain representation. Leveraging this dataset, we propose Cross-Stain Contrastive Learning (CSCL), a two-stage pretraining framework with a lightweight adapter trained using patch-wise contrastive alignment to improve the compatibility of H&E features with corresponding IHC-derived contextual cues, and slide-level representation learning with Multiple Instance Learning (MIL), which uses a cross-stain attention fusion module to integrate stain-specific patch features and a cross-stain global alignment module to enforce consistency among slide-level embeddings across different stains. Experiments on cancer subtype classification, IHC biomarker status classification, and survival prediction show consistent gains, yielding high-quality, transferable H&E slide-level representations. The code and data are available at https://github.com/lily-zyz/CSCL.