# Can Protein-Derived Knowledge Improve Pathology Foundation Models?

arXiv: https://arxiv.org/abs/2609.33178 · HTML: https://mlsanity.com/paper/2609.33178/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 16 of its 37 references that are in the map.
- First posted on arXiv 27 Sep 2026.

## Builds on (most cited first, 16 of 16)

- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Relational Knowledge Distillation](https://mlsanity.com/paper/1904.05068/) (2019)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Multimodal Whole Slide Foundation Model for Pathology](https://mlsanity.com/paper/2411.19666/) (2024)
- [PRISM: A Multi-Modal Generative Foundation Model for Slide-Level Histopathology](https://mlsanity.com/paper/2405.10254/) (2024)
- [A Multimodal Knowledge-enhanced Whole-slide Pathology Foundation Model](https://mlsanity.com/paper/2407.15362/) (2024)
- [Molecular-driven Foundation Model for Oncologic Pathology](https://mlsanity.com/paper/2501.16652/) (2025)
- [Pathologist-level classification of histologic patterns on resected lung adenocarcinoma slides with deep neural networks](https://mlsanity.com/paper/1901.11489/) (2019)
- [Predicting Axillary Lymph Node Metastasis in Early Breast Cancer Using Deep Learning on Primary Tumor Biopsy Slides](https://mlsanity.com/paper/2112.02222/) (2021)
- [Do Multiple Instance Learning Models Transfer?](https://mlsanity.com/paper/2506.09022/) (2025)
- [MiCo: Multiple Instance Learning with Context-Aware Clustering for Whole Slide Image Analysis](https://mlsanity.com/paper/2506.18028/) (2025)
- [PathNavigate: A Training-Free Pathology Agent with Surprise-Guided Scan and Shared Slide Memory for Whole-Slide Image VQA](https://mlsanity.com/paper/2605.23559/) (2026)
- [Pathryoshka: Compressing Pathology Foundation Models via Multi-Teacher Knowledge Distillation with Nested Embeddings](https://mlsanity.com/paper/2511.23204/) (2025)
- [CARE: A Molecular-Guided Foundation Model with Adaptive Region Modeling for Whole Slide Image Analysis](https://mlsanity.com/paper/2602.21637/) (2026)
- [Momentum Memory for Knowledge Distillation in Computational Pathology](https://mlsanity.com/paper/2602.21395/) (2026)
- [scpFormer: A Foundation Model for Unified Representation and Integration of the Single-Cell Proteomics](https://mlsanity.com/paper/2604.20003/) (2026)

## Abstract (arXiv)

Molecularly guided pathology foundation models (PFMs) exploit transcriptomic or proteomic information to enrich whole-slide image (WSI) representations, yet effectively leveraging large standalone molecular corpora remains challenging. First, existing molecular foundation models encode protein sequences or single-cell states, not the patient-level bulk expression profiles paired with WSIs. Second, because cross-modal supervision is restricted to paired WSI-omics samples, knowledge from standalone molecular corpora reaches the pathology encoder only indirectly, creating a paired-support bottleneck. To address these challenges, we propose a three-stage framework that decouples proteomic knowledge acquisition from cross-modal transfer, yielding ProSlide, a slide-level hierarchical pathology foundation model. First, to close the modality gap, we pretrain a Proteomic Foundation Encoder (PFE) on 12,695 sample-level bulk protein profiles using virtual profile generation and expression-space multi-view pretraining. Second, we pretrain ProSlide, a patch-region-slide encoder, to predict protein expression from paired WSI-protein samples. Third, to relax the paired-support bottleneck, we introduce Prot2Path, a cross-modal relational distillation objective. For each paired sample, it aligns the similarity distributions of the WSI and its protein profile over a shared, frozen bank of PFE-encoded paired and standalone profiles. We evaluate ProSlide on 12 downstream tasks across breast, lung, and renal cancers. Despite being pretrained with only 2,229 WSIs and 12,695 sample-level protein profiles, ProSlide achieves the highest mean accuracy and AUC within each cancer group.