SAR2Net: Learning Spatially Anchored Representations for Retrieval-Guided Cross-Stain Alignment

Achieving spatial alignment between whole-slide images (WSIs) across stains is essential for integrating morphology and molecular information, yet it remains challenging due to extreme resolution, tissue fragmentation, and large nonlinear deformations. Conventional registration pipelines depend on global pre-alignment and spatial consistency, which often collapse under such distortions. We present SAR2Net, a framework that learns spatially anchored representations and reformulates cross-stain alignment as a region-level feature retrieval problem. Instead of estimating explicit transformations, SAR2Net learns pointwise representations encoding the relative spatial relationships to tissue landmarks. Given landmarks and arbitrary coordinates, it predicts spatially anchored features that serve as deformation-invariant descriptors of tissue topology. A twostage retrieval framework then establishes correspondences between slides, even when global alignment is infeasible. Experiments on biopsy-oriented HE-IHC datasets show that SAR2Net achieves robust region-level alignment under severe tissue distortions, outperforming previous methods.