Foundation models have recently become a popular research direction within computational pathology. They are intended to be general-purpose feature extractors, promising to achieve good performance on a range of downstream tasks. Real-world pathology image data does however exhibit considerable variability. Foundation models should be robust to these variations and other distribution shifts which might be encountered in practice. We evaluate two computational pathology foundation models: UNI (trained on more than 100,000 whole-slide images) and CONCH (trained on more than 1.1 million image-caption pairs), by utilizing them as feature extractors within prostate cancer grading models. We find that while UNI and CONCH perform well relative to baselines, the absolute performance can still be far from satisfactory in certain settings. The fact that foundation models have been trained on large and varied datasets does not guarantee that downstream models always will be robust to common distribution shifts.

Prediction of mRNA gene-expression profiles directly from routine whole-slide images (WSIs) using deep learning models could potentially offer cost-effective and widely accessible molecular phenotyping. While such WSI-based gene-expression prediction models have recently emerged within computational pathology, the high-dimensional nature of the corresponding regression problem offers numerous design choices which remain to be analyzed in detail. This study provides recommendations on how deep regression models should be trained for WSI-based gene-expression prediction. For example, we conclude that training a single model to simultaneously regress all 20530 genes is a computationally efficient yet very strong baseline.