PRINTER: Deformation-Aware Adversarial Learning for Virtual IHC Staining with In Situ Fidelity

Tumor spatial heterogeneity analysis requires precise correlation between Hematoxylin and Eosin (H&E) morphology and immunohistochemical (IHC) biomarker expression, yet current methods suffer from spatial misalignment in consecutive sections, severely compromising in situ pathological interpretation. In order to obtain a more accurate virtual staining pattern, We propose PRINTER, a weakly-supervised framework that integrates PRototype-drIven content and staiNing patTERn decoupling and deformation-aware adversarial learning strategies designed to accurately learn IHC staining patterns while preserving H&E staining details. Our approach introduces three key innovations: (1) A prototype-driven staining pattern transfer with explicit content-style decoupling; and (2) A cyclic registration-synthesis framework GapBridge that bridges H&E and IHC domains through deformable structural alignment, where registered features guide cross-modal style transfer while synthesized outputs iteratively refine the registration;(3) Deformation-Aware Adversarial Learning: We propose a training framework where a generator and deformation-aware registration network jointly adversarially optimize a style-focused discriminator. Extensive experiments demonstrate that PRINTER effectively achieves superior performance in preserving H&E staining details and virtual staining fidelity, outperforming state-of-the-art methods. Our work provides a robust and scalable solution for virtual staining, advancing the field of computational pathology.