PGVMS: A Prompt-Guided Unified Framework for Virtual Multiplex IHC Staining with Pathological Semantic Learning

2026-02-26Computer Vision and Pattern Recognition

Computer Vision and Pattern Recognition
AI summary

The authors developed a new computer method to digitally create multiple protein stain images from a single standard tissue image, helping when there isn't enough tissue for many tests. They tackled three main problems: giving better instructions to guide the staining, keeping the protein patterns accurate, and fixing alignment issues between different stains. Their approach uses smart prompts, a way to check protein patterns directly, and a method to align images better. This aims to improve virtual staining using only single-stain training data.

Immunohistochemical stainingVirtual multiplex stainingProtein expressionPathological visual language modelAdaptive prompt guidanceProtein-aware learningPrototype-consistent learningSpatial alignmentDigital pathologyUniplex training data
Authors
Fuqiang Chen, Ranran Zhang, Wanming Hu, Deboch Eyob Abera, Yue Peng, Boyun Zheng, Yiwen Sun, Jing Cai, Wenjian Qin
Abstract
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).