PD46-05 GENETIC ABERRATIONS IDENTIFIED IN FOCAL BARBOTAGES– a COMPLEMENTARY DIAGNOSTIC TOOL IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD46-05 GENETIC ABERRATIONS IDENTIFIED IN FOCAL BARBOTAGES– a COMPLEMENTARY DIAGNOSTIC TOOL IN UPPER TRACT UROTHELIAL CARCINOMA (UTUC) Tomas Axelsson, Filip Sydén, Jesper Eisfeldt, Ylva Eriksson, Gustav Göthner Lundberg, Alexandra Grahn, Emma Tham, and Marianne Brehmer Tomas AxelssonTomas Axelsson More articles by this author , Filip SydénFilip Sydén More articles by this author , Jesper EisfeldtJesper Eisfeldt More articles by this author , Ylva ErikssonYlva Eriksson More articles by this author , Gustav Göthner LundbergGustav Göthner Lundberg More articles by this author , Alexandra GrahnAlexandra Grahn More articles by this author , Emma ThamEmma Tham More articles by this author , and Marianne BrehmerMarianne Brehmer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: UTUC is divided into low- and high risk UTUC. Despite radical surgery, 10-20% in the low-risk and 50% of the patients in the high-risk group respectively, recur and die from UTUC. Although tumour stage and grade are known prognostic factors, the mechanisms of recurrence in each risk group respectively are not entirely known. In a previous study of genetic analysis of tumour tissue from nephroureterectomy (NU) we showed that gene mutations in some cases had a stronger prognostic value than histopathology. We have also previously shown that cytology taken as focal barbotage, at ureterorenoscopy (URS), renders good diagnostic material. The aim of this study was to investigate if gene analysis of focal barbotages obtained at URS is possible. In addition, we tried to identify gene mutations and copy number variations (CNV) that might signify a more aggressive tumour. METHODS: This prospective study included 41 patients with UTUC confirmed at URS from 2018 to 2021. Patients were followed until October 2022. At URS, barbotage specimens from the ureter and renal pelvis were collected and sent for cytology analysis and for gene sequencing. When possible, tumour biopsies were taken. Final tumour grades (WHO-classifications 1999 and 2004) were determined from cytology and/or biopsy, or from radical NU samples when available. A total of 41 barbotage samples were sent for genetic analysis. Next generation sequencing using a 388-gene panel was performed. Manual filtering of the sequencing data from each sample was performed to identify possible pathogenic mutations. CNV was analysed using WisecondorX. RESULTS: 41 patients, 26 men and 15 women were included. Mean age at inclusion was 75 years. In 14 patients the tumour was low grade (8 G1, 5 G2 and one unclear) and in 27 patients the tumour was high grade (14 G2 and 13 G3). During the follow-up period, 5 patients died from UTUC and 7 patients had tumour progression. Out of 41 focal barbotages analysed we identified known and suspected pathogenic mutations in 39 and CNVs in 32. Known pathogenic mutations in the fibroblast growth receptor 3 (FGFR3) gene were common in grade 1 and 2 tumours but not present in any G3 tumour. No patients with a FGFR3 mutation died during follow-up. Seven patients had a pathogenic mutation in tumour protein 53 (TP53), 6 of these had high grade tumours, 2 of whom died from UTUC during follow-up. One patient with a TP53 mutation had a low grade, G1-tumor, that progressed with metastasis during follow up. CONCLUSIONS: Gene mutations and CNVs can be identified in focal barbotage samples obtained at URS and may be complementary to cytologic analysis. The technique may be helpful in identifying low risk tumours that might be more at risk for disease progression or death than previously thought. Source of Funding: Nothing to declare © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1171 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tomas Axelsson More articles by this author Filip Sydén More articles by this author Jesper Eisfeldt More articles by this author Ylva Eriksson More articles by this author Gustav Göthner Lundberg More articles by this author Alexandra Grahn More articles by this author Emma Tham More articles by this author Marianne Brehmer More articles by this author Expand All Advertisement PDF downloadLoading ...