Cross-Stain Contrastive Learning for Paired Immunohistochemistry and Histopathology Slide Representation LearningYizhi Zhang, Lei Fan, Zhulin Tao et al.
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.
Boundary-Guided Learning for Gene Expression Prediction in Spatial TranscriptomicsMingcheng Qu, Yuncong Wu, Donglin Di et al.
Spatial transcriptomics (ST) has emerged as an advanced technology that provides spatial context to gene expression. Recently, deep learning-based methods have shown the capability to predict gene expression from WSI data using ST data. Existing approaches typically extract features from images and the neighboring regions using pretrained models, and then develop methods to fuse this information to generate the final output. However, these methods often fail to account for the cellular structure similarity, cellular density and the interactions within the microenvironment. In this paper, we propose a framework named BG-TRIPLEX, which leverages boundary information extracted from pathological images as guiding features to enhance gene expression prediction from WSIs. Specifically, our model consists of three branches: the spot, in-context and global branches. In the spot and in-context branches, boundary information, including edge and nuclei characteristics, is extracted using pretrained models. These boundary features guide the learning of cellular morphology and the characteristics of microenvironment through Multi-Head Cross-Attention. Finally, these features are integrated with global features to predict the final output. Extensive experiments were conducted on three public ST datasets. The results demonstrate that our BG-TRIPLEX consistently outperforms existing methods in terms of Pearson Correlation Coefficient (PCC). This method highlights the crucial role of boundary features in understanding the complex interactions between WSI and gene expression, offering a promising direction for future research.
Multimodal Cancer Survival Analysis via Hypergraph Learning with Cross-Modality RebalanceMingcheng Qu, Guang Yang, Donglin Di et al.
Multimodal pathology-genomic analysis has become increasingly prominent in cancer survival prediction. However, existing studies mainly utilize multi-instance learning to aggregate patch-level features, neglecting the information loss of contextual and hierarchical details within pathology images. Furthermore, the disparity in data granularity and dimensionality between pathology and genomics leads to a significant modality imbalance. The high spatial resolution inherent in pathology data renders it a dominant role while overshadowing genomics in multimodal integration. In this paper, we propose a multimodal survival prediction framework that incorporates hypergraph learning to effectively capture both contextual and hierarchical details from pathology images. Moreover, it employs a modality rebalance mechanism and an interactive alignment fusion strategy to dynamically reweight the contributions of the two modalities, thereby mitigating the pathology-genomics imbalance. Quantitative and qualitative experiments are conducted on five TCGA datasets, demonstrating that our model outperforms advanced methods by over 3.4\% in C-Index performance.