用H&E图像预测IHC分子标志物,节省病理检测成本
Cross-Modality Learning for Predicting IHC Biomarkers from H&E-Stained Whole-Slide Images
- 通过对比学习对齐H&E与IHC图像的形态与分子特征
- 在胃肠道和肺部组织上对三种IHC标志物预测准确率达72%-83%
- 无需配准或逐块标注,适合临床预筛使用
苏木精-伊红(H&E)染色是病理分析的核心,可清晰呈现细胞形态与组织结构,用于癌症诊断、分型与分级。免疫组化(IHC)染色则能检测特定蛋白,提供分子信息,提升诊断精度并指导治疗。然而,IHC染色成本高、耗时长且需专业资源。为此,本文提出HistoStainAlign框架,通过联合学习形态与分子特征,直接从H&E全切片图像(WSIs)预测IHC染色模式。该框架采用对比学习策略融合成对的H&E与IHC嵌入,捕捉跨染色模态的互补特征,无需局部标注或组织配准。在胃肠道及肺部组织的WSIs上评估了三种常见IHC染色(P53、PD-L1、Ki-67),加权F1分数分别为0.735(95% CI: 0.670–0.799)、0.830(95% CI: 0.772–0.886)、0.723(95% CI: 0.607–0.836)。嵌入分析表明对比对齐有效捕获了有意义的跨染色关系。与基线模型对比进一步验证了对比学习在提升染色模式预测性能上的优势。本研究展示了计算方法作为预筛工具的潜力,有助于优化IHC检测流程,提高效率。
原文摘要 · Abstract (English)
Hematoxylin and Eosin (H&E) staining is a cornerstone of pathological analysis, offering reliable visualization of cellular morphology and tissue architecture for cancer diagnosis, subtyping, and grading. Immunohistochemistry (IHC) staining provides molecular insights by detecting specific proteins within tissues, enhancing diagnostic accuracy, and improving treatment planning. However, IHC staining is costly, time-consuming, and resource-intensive, requiring specialized expertise. To address these limitations, this study proposes HistoStainAlign, a novel deep learning framework that predicts IHC staining patterns directly from H&E whole-slide images (WSIs) by learning joint representations of morphological and molecular features. The framework integrates paired H&E and IHC embeddings through a contrastive training strategy, capturing complementary features across staining modalities without patch-level annotations or tissue registration. The model was evaluated on gastrointestinal and lung tissue WSIs with three commonly used IHC stains: P53, PD-L1, and Ki-67. HistoStainAlign achieved weighted F1 scores of 0.735 [95% Confidence Interval (CI): 0.670-0.799], 0.830 [95% CI: 0.772-0.886], and 0.723 [95% CI: 0.607-0.836], respectively for these three IHC stains. Embedding analyses demonstrated the robustness of the contrastive alignment in capturing meaningful cross-stain relationships. Comparisons with a baseline model further highlight the advantage of incorporating contrastive learning for improved stain pattern prediction. This study demonstrates the potential of computational approaches to serve as a pre-screening tool, helping prioritize cases for IHC staining and improving workflow efficiency.
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