Immunohistochemical (IHC) virtual staining is a task that generates virtual IHC images from H&E images while maintaining pathological semantic consistency with adjacent slices. This task aims to achieve cross-domain mapping between morphological structures and staining patterns through generative models, providing an efficient and cost-effective solution for pathological analysis. However, under weakly paired conditions, spatial heterogeneity between adjacent slices presents significant challenges. This can lead to inaccurate one-to-many mappings and generate results that are inconsistent with the pathological semantics of adjacent slices. To address this issue, we propose a novel unbalanced self-information feature transport for IHC virtual staining, named USIGAN, which extracts global morphological semantics without relying on positional correspondence. By removing weakly paired terms in the joint marginal distribution, we effectively mitigate the impact of weak pairing on joint distributions, thereby significantly improving the content consistency and pathological semantic consistency of the generated results. Moreover, we design the Unbalanced Optimal Transport Consistency Mining (UOT-CTM) mechanism and the Pathology Self-Correspondence Mining (PC-SCM) mechanism to construct correlation matrices between H&E and generated IHC in image-level and real IHC and generated IHC image sets in intra-group level. Experiments conducted on two publicly available datasets demonstrate that our method achieves superior performance across multiple clinically significant metrics, such as IoD and Pearson-R correlation, demonstrating better clinical relevance. The code is available at: https://github.com/MIXAILAB/USIGAN.

Immunohistochemical (IHC) staining enables precise molecular profiling of protein expression, with over 200 clinically available antibody-based tests in modern pathology. However, comprehensive IHC analysis is frequently limited by insufficient tissue quantities in small biopsies. Therefore, virtual multiplex staining emerges as an innovative solution to digitally transform H&E images into multiple IHC representations, yet current methods still face three critical challenges: 1) inadequate semantic guidance for multi-staining, 2) inconsistent distribution of immunochemistry staining, and 3) spatial misalignment across different stain modalities. To overcome these limitations, we present a prompt-guided framework for virtual multiplex IHC staining using only uniplex training data (PGVMS). Our framework introduces three key innovations corresponding to each challenge: First, an adaptive prompt guidance mechanism employing a pathological visual language model dynamically adjusts staining prompts to resolve semantic guidance limitations (Challenge 1). Second, our protein-aware learning strategy (PALS) maintains precise protein expression patterns by direct quantification and constraint of protein distributions (Challenge 2). Third, the prototype-consistent learning strategy (PCLS) establishes cross-image semantic interaction to correct spatial misalignments (Challenge 3). Evaluated on two benchmark datasets, PGVMS demonstrates superior performance in pathological consistency. In general, PGVMS represents a paradigm shift from dedicated single-task models toward unified virtual staining systems.