To investigate gene alterations as diagnostic and prognostic markers in upper tract urothelial carcinoma (UTUC).
Patients with UTUC who underwent nephroureterectomy in 2005-2012 were followed until November 2020. DNA was extracted from paraffin-embedded tumour tissue. Next-generation sequencing using a 388-gene panel was performed. First a blinded analysis using principal component analysis and hierarchical clustering was used to search for patterns of mutations. Then a comparative analysis using ANOVA was used to search for mutations enriched in groups of various grade, stage and survival. In addition, careful manual annotation was used to identify pathogenic mutations overrepresented in tumours of high grade/stage and/or poor survival.
39 patients were included. All tumour stages and grades were represented in the cohort. The median follow-up was 10.6 years. Eleven patients died from UTUC during the follow-up time. Tumour mutational burden showed a statistically significant correlation with stage, grade and stage + grade. G1, G2 and G3 tumours had different mutational patterns. Patients who died from UTUC had pathogenic mutations in specific genes e.g. TP53 and HRAS. Patients with TaG1 tumours with a known pathogenic FGFR3 mutation did not die of UTUC.
The genetic analysis was highly concordant with histopathological features and added prognostic information in some cases. Thus, results from genomic profiling may contribute to the choice of treatment and follow-up regimens in the future.
BJU international. 2021 Aug 10 [Epub ahead of print]
Alexandra Grahn, Jesper Eisfeldt, Camilla Malm, Hassan Foroughi Asl, Georg Jaremko, Emma Tham, Marianne Brehmer
Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden., Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden., Genomic Medicine Center, Karolinska University Hospital, Stockholm, Sweden., Department of Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden., Department of Clinical Sciences, Karolinska Institutet, Stockholm, Sweden.