Axelsson Tomas Andri, Sydén Filip, Eisfeldt Jesper, Eriksson Ylva, Lundberg Gustav Göthner, Jaremko Georg, Gyllensten Ollanta Cuba, Tham Emma, Brehmer Marianne
Division of Urology, Danderyd Hospital, Stockholm, Sweden.
Department of Urology, Stockholm South General Hospital, Stockholm, Sweden.
BJU Int. 2025 May;135(5):792-801. doi: 10.1111/bju.16620. Epub 2024 Dec 9.
To investigate whether genetic analysis of focal barbotage samples obtained at ureterorenoscopy (URS) is possible, and to identify genetic aberrations that might add prognostic information.
This prospective study included barbotage samples from 42 patients with upper urinary tract urothelial carcinoma (UTUC) confirmed at URS. At URS, focal barbotage specimens were collected for cytology and for gene sequencing. Tumour grades were determined from cytology and/or biopsy, or from radical nephroureterectomy samples. Next-generation sequencing using a 385-gene panel was performed and single nucleotide variants (SNVs), deletions/insertions (indels) and copy number aberrations (CNAs) were identified. Manual filtering of the SNVs/indels was performed to identify possible pathogenic mutations.
Of the 42 samples, two failed quality control, therefore, 40 focal barbotage samples were sequenced. We identified known and suspected pathogenic mutations and other genomic aberrations in 36 samples. The most common variants were in TERT (78%), FGFR3 (50%), KMT2D (42%), KDM6A (42%), ARID1A (39%), TP53 (19%) and deletion of 9q (50%). Known pathogenic mutations in FGFR3 were common in grade 1 and 2 tumours, but not present in any grade 3 tumour. No patients with an FGFR3 mutation died during follow-up. TP53 variants or deletions, as well as amplifications of MDM2, were only present in high-grade (HG) tumours or low-grade (LG) tumours in patients who had metastasis/died from urinary tract carcinoma. CNAs were detected in 36/40 barbotage samples, 91% of the HG samples and 69% of the LG samples, including those from all five patients with LG tumours with metastasis or who died from urinary tract cancer.
Focal barbotage samples enable identification of gene mutations and other genetic aberrations that may add important prognostic information to histopathology and cytology. Refined prognostication of UTUC patients already at diagnosis can guide treatment decisions and follow-up programmes.
探讨在输尿管肾镜检查（URS）时获取的局灶灌洗样本进行基因分析是否可行，并识别可能增加预后信息的基因变异。
这项前瞻性研究纳入了42例经URS确诊的上尿路尿路上皮癌（UTUC）患者的灌洗样本。在URS时，收集局灶灌洗标本用于细胞学检查和基因测序。肿瘤分级通过细胞学检查和/或活检，或根治性肾输尿管切除术样本确定。使用385个基因的面板进行二代测序，识别单核苷酸变异（SNV）、缺失/插入（indel）和拷贝数变异（CNA）。对SNV/indel进行人工筛选以识别可能的致病突变。
42个样本中，2个未通过质量控制，因此，对40个局灶灌洗样本进行了测序。我们在36个样本中识别出已知和疑似致病突变以及其他基因组变异。最常见的变异存在于TERT（78%）、FGFR3（50%）、KMT2D（42%）、KDM6A（42%）、ARID1A（39%）、TP53（19%）以及9号染色体长臂缺失（50%）。FGFR3中的已知致病突变在1级和2级肿瘤中常见，但在任何3级肿瘤中均未出现。随访期间，没有FGFR3突变的患者死亡。TP53变异或缺失以及MDM2扩增仅存在于发生转移/死于尿路癌的患者的高级别（HG）肿瘤或低级别（LG）肿瘤中。在36/40个灌洗样本中检测到CNA，91%的HG样本和69%的LG样本中存在CNA，包括所有5例发生转移或死于尿路癌的LG肿瘤患者的样本。
局灶灌洗样本能够识别基因突变和其他基因变异，这些变异可能为组织病理学和细胞学增加重要的预后信息。对UTUC患者在诊断时进行精准的预后评估可以指导治疗决策和随访计划。
