Artificial Intelligence to Predict the BRAF V595E Mutation in Canine Urinary Bladder Urothelial Carcinomas

SIMPLE SUMMARY: In canine urothelial carcinoma, the BRAF gene is frequently mutated (V595E). To detect this mutation, urine or tissue samples are currently tested by PCR. Recent advances in digital pathology and the power of artificial intelligence (AI) have opened up new possibilities for the detection of genetic alterations through AI histology. This new approach offers a wide range of new opportunities in the field of diagnostic and predictive tumour marker detection. The aim of this study was to test the efficacy of AI histology to predict the presence of the BRAF mutation in canine bladder carcinomas and to assess its intratumoral heterogeneity. This is the first study to utilise AI histology to predict BRAF mutational status in canine urothelial cell carcinomas. ABSTRACT: In dogs, the BRAF mutation (V595E) is common in bladder and prostate cancer and represents a specific diagnostic marker. Recent advantages in artificial intelligence (AI) offer new opportunities in the field of tumour marker detection. While AI histology studies have been conducted in humans to detect BRAF mutation in cancer, comparable studies in animals are lacking. In this study, we used commercially available AI histology software to predict BRAF mutation in whole slide images (WSI) of bladder urothelial carcinomas (UC) stained with haematoxylin and eosin (HE), based on a training (n = 81) and a validation set (n = 96). Among 96 WSI, 57 showed identical PCR and AI-based BRAF predictions, resulting in a sensitivity of 58% and a specificity of 63%. The sensitivity increased substantially to 89% when excluding small or poor-quality tissue sections. Test reliability depended on tumour differentiation (p < 0.01), presence of inflammation (p < 0.01), slide quality (p < 0.02) and sample size (p < 0.02). Based on a small subset of cases with available adjacent non-neoplastic urothelium, AI was able to distinguish malignant from benign epithelium. This is the first study to demonstrate the use of AI histology to predict BRAF mutation status in canine UC. Despite certain limitations, the results highlight the potential of AI in predicting molecular alterations in routine tissue sections.