Deep learning-based predictions of clear and eosinophilic phenotypes in clear cell renal cell carcinoma

We have recently shown that histological phenotypes focusing on clear and eosinophilic cytoplasm in clear cell renal cell carcinoma (ccRCC) correlated with prognosis and the response to angiogenesis inhibition and checkpoint blockade. This study aims to objectively show the diagnostic utility of clear or eosinophilic phenotypes of ccRCC by developing an artificial intelligence (AI) model using the TCGA-ccRCC dataset and to demonstrate if the clear or eosinophilic predicted phenotypes correlate with pathological factors and gene signatures associated with angiogenesis and cancer immunity. Before the development of the AI model, histological evaluation using hematoxylin and eosin whole-slide images of the TCGA-ccRCC cohort (n = 435) was performed by a urologic pathologist. The AI model was developed as follows. First, the highest-grade area on each whole slide image was captured for image processing. Second, the selected regions were cropped into tiles. Third, the AI model was trained using transfer learning on a deep convolutional neural network, and clear or eosinophilic predictions were scaled as AI scores. Next, we verified the AI model using a validation cohort (n = 95). Finally, we evaluated the accuracy of the prognostic predictions of the AI model and revealed that the AI model detected clear and eosinophilic phenotypes with high accuracy. The AI model stratified the patients' outcomes, and the predicted eosinophilic phenotypes correlated with adverse clinicopathological characteristics and high immune-related gene signatures. In conclusion, the AI-based histologic subclassification accurately predicted clear or eosinophilic phenotypes of ccRCC, allowing for consistently reproducible stratification for prognostic and therapeutic stratification.