Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY.
Urol Oncol. 2023 Oct;41(10):433.e19-433.e24. doi: 10.1016/j.urolonc.2023.07.007. Epub 2023 Aug 26.
There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor.
In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated).
Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (n = 34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue.
Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.
目前，准确诊断和临床分期上尿路上皮癌（UTUC）的能力有限。最容易获得和广泛使用的尿生物标志物是尿细胞学，它评估细胞物质，但缺乏敏感性。我们试图评估在上尿路上皮癌患者的尿细胞学标本上进行下一代测序（NGS）的可行性，并评估与原发性肿瘤组织的基因组一致性。
在这项回顾性研究中，我们确定了 2019 年至 2022 年期间在纪念斯隆凯特琳癌症中心（MSK）治疗的 48 名 UTUC 患者，他们有已保存或新鲜的尿液样本。当有匹配的、先前测序的肿瘤组织时，使用方便队列。尿液标本经过处理，包括沉淀的无细胞 DNA 在内的剩余物质使用我们的肿瘤无偏见、靶向外显子组测序平台进行测序，该平台评估 505 个与癌症相关的基因（MSK-IMPACT）。主要结果是至少在尿液细胞学标本中检测到 1 个可检测的突变。次要结果是与匹配组织的一致性（使用 ANOVA 或 Chi-Square，视情况而定）。
48 例尿液细胞学患者样本中的 45 例（94%）成功进行了基因组测序。最常见的突变是 TERT（62.2%）、KMT2D（46.7%）和 FGFR3（35.6%）。所有阴性尿液细胞学和低级别组织的患者均成功进行了细胞学测序。在 45 例患者中，有 36 例有匹配的肿瘤组织可用；总的来说，与匹配组织的一致性为 55%（总共确定的 238 个致癌或可能致癌的体细胞突变中有 131 个）。然而，在 94.4%（n=34/36）的患者中，细胞学与组织至少有 1 个共同突变。11 例（30.6%）患者的细胞学与组织完全一致。
对选择性 UTUC 细胞学的尿标本进行测序在上尿路上皮癌患者中几乎都是可行的。正在进行前瞻性研究以调查这项有前途的技术的临床作用。
