Joint modeling histology and molecular markers for cancer classification

Cancers are characterized by remarkable heterogeneity and diverse prognosis. Accurate cancer classification is essential for patient stratification and clinical decision-making. Although digital pathology has been advancing cancer diagnosis and prognosis, the paradigm in cancer pathology has shifted from purely relying on histology features to incorporating molecular markers. There is an urgent need for digital pathology methods to meet the needs of the new paradigm. We introduce a novel digital pathology approach to jointly predict molecular markers and histology features and model their interactions for cancer classification. Firstly, to mitigate the challenge of cross-magnification information propagation, we propose a multi-scale disentangling module, enabling the extraction of multi-scale features from high-magnification (cellular-level) to low-magnification (tissue-level) whole slide images. Further, based on the multi-scale features, we propose an attention-based hierarchical multi-task multi-instance learning framework to simultaneously predict histology and molecular markers. Moreover, we propose a co-occurrence probability-based label correlation graph network to model the co-occurrence of molecular markers. Lastly, we design a cross-modal interaction module with the dynamic confidence constrain loss and a cross-modal gradient modulation strategy, to model the interactions of histology and molecular markers. Our experiments demonstrate that our method outperforms other state-of-the-art methods in classifying glioma, histology features and molecular markers. Our method promises to promote precise oncology with the potential to advance biomedical research and clinical applications. The code is available at github.