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

Author:

Küchler Leonore1ORCID,Posthaus Caroline1,Jäger Kathrin23,Guscetti Franco4ORCID,van der Weyden Louise5ORCID,von Bomhard Wolf6,Schmidt Jarno M.7,Farra Dima8ORCID,Aupperle-Lellbach Heike23ORCID,Kehl Alexandra23ORCID,Rottenberg Sven1910ORCID,de Brot Simone1910ORCID

Affiliation:

1. Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland

2. Laboklin GmbH & Co. KG, 97688 Bad Kissingen, Germany

3. Institute of Pathology, Department of Comparative Experimental Pathology, School of Medicine, Technical University of Munich, 81675 Munich, Germany

4. Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zurich, 8057 Zurich, Switzerland

5. Wellcome Sanger Institute, Cambridge CB10 1SA, UK

6. Synlab Vet Animal Pathology Munich, 81477 Munich, Germany

7. Small Animal Clinic Hofheim, 65719 Hofheim, Germany

8. Veterinary Public Health Institute, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland

9. COMPATH, Vetsuisse Faculty, University of Bern, 3012 Bern, Switzerland

10. Bern Center for Precision Medicine, University of Bern, 3008 Bern, Switzerland

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.

Funder

University of Bern

Albert Heim Foundation

Publisher

MDPI AG

Subject

General Veterinary,Animal Science and Zoology

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