BRAFV595E mutation detected across the disease spectrum from non-neoplastic urothelium to invasive urothelial carcinoma in dogs.

Abstract

Objective The goal was to determine the presence of a driver mutation in dogs with and without detectable cancer to set the stage for future cancer prevention research exploiting processes that inhibit cancer development in the presence of such mutations. The objective was to detect the v-raf murine sarcoma viral oncogene homolog B (BRAF) mutation BRAFV595E across the disease spectrum from non-neoplastic urothelium to invasive urothelial carcinoma (UC) in dogs. Methods Scottish Terriers ≥ 6 years old with no outward evidence of urinary disease (n = 120) were screened for UC by urinalysis, urinary tract ultrasonography, follow-up cystoscopic biopsy, and necropsy when possible. Initial results were published in 2022. Extended follow-up is presented here. The BRAFV595E mutation was detected in urine sediment by droplet digital PCR and in bladder tissues by immunohistochemistry. Results For 120 dogs screened, biopsy-confirmed UC was found in 41 dogs including 31 high-grade UC, 6 low-grade UC, 1 carcinoma in situ, and 3 dysplasias that progressed to high-grade UC. The BRAFV595E mutation was found in the urine of 23 of 26 dogs with high-grade UC, 4 of 5 dogs with low-grade UC, 2 of 3 dogs with dysplasia, and 12 of 66 dogs with no UC detected over a median of 14 months of follow-up (range, 4 to 71 months). The BRAFV595E mutation was detected in UC and non-neoplastic urothelium by immunohistochemistry. Conclusions The BRAFV595E mutation is present in various stages of canine UC and non-neoplastic urothelium. This knowledge will contribute to future cancer prevention research. Clinical Relevance Urothelial carcinoma screening should be implemented for Scottish Terriers and potentially dogs in other high-risk breeds. Biopsy and standardized imaging remain essential in UC management.