Papers for
clinical pathology teams
Papers whose findings have a practical use for this group, as judged from the abstract. Open a paper to read what it means in practice.
Deep learning predicts colon cancer survival using tissue morphology
Morphology-aware deep learning predicts colorectal cancer survival from whole-slide images
Abstract: Background: Five-year survival prediction from hematoxylin-and-eosin whole-slide images could support risk stratification, but the task is weakly supervised, and the tissue morphologies carrying prognostic information remain incompletely characterized. Methods: We conducted a retrospective secondary analysis using TCGA-COAD/READ (n=562) for morphology-specific analysis, Alliance/ CALGB 89803 (n=424) for model development, and SurGen (n=218) for external evaluation. We propose MorphContrast, a morphology-aware contrastive multiple-instance learning framework that uses tissue labels as structural supervision for five-year survival prediction. MorphContrast combines gated-attention pooling with three auxiliary objectives: patch-level morphology labels define within-patient contrasts, outcome concordance or discordance defines cross-patient contrasts within matched morphologies, and diversity regularization discourages representational collapse. Morphology-matched patches from patients with discordant outcomes serve as hard negatives, encouraging prognostic discrimination within comparable histologic contexts. Results: Morphology-specific models show weak but distributed prognostic discrimination: adipose tissue achieves an area under the receiver operating characteristic curve (AUC) of 0.622, stroma achieves 0.604, and both perform comparably to tumor epithelium (0.601-0.605). On Alliance/CALGB 89803, the single model achieves an AUC of 0.642, while the post hoc ensemble reaches a pooled out-of-fold AUC of 0.70 and a risk-group hazard ratio of 3.79 (95% confidence interval: 2.55-5.63). On the external SurGen colon cancer cohort (n=218), the single model and ensemble achieve AUCs of 0.669 and 0.678, respectively. Conclusions: These findings support tissue morphology as structural supervision for outcome-aware representation learning in colorectal cancer prognosis.
Tumor immune patterns improve cross cancer biomarker prediction accuracy
TIRA: Tumor Immune Representation Adaptation for Zero-Shot Cross-Cancer MSI and TMB Prediction
Abstract: Microsatellite instability-high (MSI-H) and high tumor mutational burden (TMB-H) are clinically relevant biomarkers, yet their histopathological prediction remains challenging when models are transferred across morphologically distinct cancer types. Immune-associated spatial patterns can persist across cancers despite these morphological differences, but foundation-model-based predictors trained on a single cancer do not explicitly use this information, limiting cross-cancer generalization. To address this limitation, we propose TIRA (Tumor Immune Representation Adaptation), a target-free framework that refines frozen foundation-model representations using spatial immune topology, without requiring target-domain data during model development or test-time adaptation. TIRA uses a topology-supervised biology representation to condition tile-level attention while pooling only morphological features for joint MSI and TMB prediction. We train TIRA on TCGA-COAD+READ and evaluate it zero-shot on CPTAC-COAD, TCGA-STAD, TCGA-UCEC, and CPTAC-UCEC, covering cross-site, cross-cancer, and combined cross-cancer-site distribution shifts under UNI2, CONCH, and Virchow2. With UNI2, TIRA improved zero-shot AUROC on TCGA-STAD from 0.633 to 0.766 for MSI and from 0.651 to 0.772 for TMB. Source-derived spatial immune topology improved the cross-cancer robustness of frozen pathology foundation-model representations.
Image based gene ranking improves gene discovery in tissue analysis
Preserving DEG Rankings for Gene Discovery in Histology-Based Spatial Gene Expression Prediction
Abstract: Predicting spatial gene expression from histology images could scale spatial transcriptomics (ST) to image-only cohorts, but conventional histology-based ST prediction is trained and evaluated mainly by per-gene spatial-profile reconstruction. This objective is misaligned with a key downstream use of ST: differentially expressed gene (DEG) discovery, where genes are ranked for a biological or morphology-defined contrast by evidence of between-group expression differences. We formulate image-based differential expression ranking (IDER), which asks whether predicted expression profiles preserve the contrast-specific ranked gene list obtained from measured profiles. IDER compares gene rankings induced by differential-expression statistics, rather than raw expression magnitudes or per-gene spatial correlations. We further introduce a differentiable IDER objective that aligns these statistics across genes and can be trained with morphology-derived proxy contrasts without predefined biological group labels. Experiments on public ST datasets show improved DEG-ranking agreement and pathway-enrichment overlap over conventional reconstruction objectives, including morphology-derived and pathologist-annotated tissue-region evaluations.