Evaluation of a Cytology-Molecular Co-Test in Liquid-Based Cytology-Processed Urine for Defining Indeterminate Categories of the Paris System.

IF 1.6 4区医学 Q3 PATHOLOGY

Acta Cytologica Pub Date : 2024-09-23 DOI:10.1159/000541578

Maria Samara, Eleni Thodou, Christina Apostolopoulou, Panagiotis J Vlachostergios, Lampros Mitrakas, Ioannis Zachos, Maria Anagnostou, George Koukoulis, Vassilios Tzortzis

{"title":"Evaluation of a Cytology-Molecular Co-Test in Liquid-Based Cytology-Processed Urine for Defining Indeterminate Categories of the Paris System.","authors":"Maria Samara, Eleni Thodou, Christina Apostolopoulou, Panagiotis J Vlachostergios, Lampros Mitrakas, Ioannis Zachos, Maria Anagnostou, George Koukoulis, Vassilios Tzortzis","doi":"10.1159/000541578","DOIUrl":null,"url":null,"abstract":"Introduction: Urine cytology using the Paris system (TPS) classification is useful for the detection and monitoring of bladder urothelial carcinoma (UC). However, the categories \"atypical urothelial cells\" (AUCs) and \"suspicious for high-grade urothelial carcinoma\" (SHGUC) do not establish a clear diagnosis. This pilot study aimed to investigate whether the presence of mutations in fibroblast growth factor receptor 3 (FGFR3) and telomerase reverse transcriptase (TERT) genes, in urine processed with liquid-based cytology (LBC) could enhance the diagnostic performance of cytology, particularly in defining the indeterminate categories of AUC and SHGUC.Methods: Urine samples from 82 UC patients with primary tumors or under surveillance and 10 healthy individuals were examined. The ThinPrep method was used for cytology followed by DNA isolation from urine sediments. Targeted molecular analysis was achieved in 70 cases (63 patients and 7 controls) for exons 7 and 10 of the FGFR3 gene and the TERT gene promoter (pTERT), using PCR and Sanger sequencing. Molecular results were correlated with TPS cytology categories and validated by histopathological findings following cystoscopy.Results: In healthy subjects, cytology was negative for high-grade urothelial carcinoma (NHGUC) and no mutations were found. No mutations were found in patients with NHGUC cytology, except for one case with equivocal cystoscopy that carried a pTERT mutation. In high-grade urothelial carcinoma cytology (HGUC) (15/20, 75%) of the cases with histologically confirmed UC, molecular analysis revealed the presence of pTERT without FGFR3 mutations. In SHGUC and AUC cytology, FGFR3 and/or pTERT mutations were detected in 3/4 (75%) and 4/4 (100%) histologically confirmed UC cases, respectively. Cytology sensitivity was 85.7% increasing to 100% with the combined cytology-molecular test, whereas specificity remained unchanged at 86.3%.Conclusions: This pilot study suggests that the incorporation of FGFR3/pTERT molecular testing in urine LBC could enhance the diagnostic value of cytology by diagnosing bladder urothelial carcinoma in indeterminate cytology categories.","PeriodicalId":6959,"journal":{"name":"Acta Cytologica","volume":" ","pages":"1-12"},"PeriodicalIF":1.6000,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Cytologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1159/000541578","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PATHOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Introduction: Urine cytology using the Paris system (TPS) classification is useful for the detection and monitoring of bladder urothelial carcinoma (UC). However, the categories "atypical urothelial cells" (AUCs) and "suspicious for high-grade urothelial carcinoma" (SHGUC) do not establish a clear diagnosis. This pilot study aimed to investigate whether the presence of mutations in fibroblast growth factor receptor 3 (FGFR3) and telomerase reverse transcriptase (TERT) genes, in urine processed with liquid-based cytology (LBC) could enhance the diagnostic performance of cytology, particularly in defining the indeterminate categories of AUC and SHGUC.

Methods: Urine samples from 82 UC patients with primary tumors or under surveillance and 10 healthy individuals were examined. The ThinPrep method was used for cytology followed by DNA isolation from urine sediments. Targeted molecular analysis was achieved in 70 cases (63 patients and 7 controls) for exons 7 and 10 of the FGFR3 gene and the TERT gene promoter (pTERT), using PCR and Sanger sequencing. Molecular results were correlated with TPS cytology categories and validated by histopathological findings following cystoscopy.

Results: In healthy subjects, cytology was negative for high-grade urothelial carcinoma (NHGUC) and no mutations were found. No mutations were found in patients with NHGUC cytology, except for one case with equivocal cystoscopy that carried a pTERT mutation. In high-grade urothelial carcinoma cytology (HGUC) (15/20, 75%) of the cases with histologically confirmed UC, molecular analysis revealed the presence of pTERT without FGFR3 mutations. In SHGUC and AUC cytology, FGFR3 and/or pTERT mutations were detected in 3/4 (75%) and 4/4 (100%) histologically confirmed UC cases, respectively. Cytology sensitivity was 85.7% increasing to 100% with the combined cytology-molecular test, whereas specificity remained unchanged at 86.3%.

Conclusions: This pilot study suggests that the incorporation of FGFR3/pTERT molecular testing in urine LBC could enhance the diagnostic value of cytology by diagnosing bladder urothelial carcinoma in indeterminate cytology categories.

查看原文本刊更多论文

评估液体细胞学处理尿液中的细胞学-分子联合检测，以确定巴黎系统的不确定类别。

简介：采用巴黎系统（TPS）分类的尿液细胞学检查有助于检测和监测膀胱尿路上皮癌（UC）。然而，"非典型尿路上皮细胞"（AUC）和 "疑似高级别尿路上皮癌"（SHGUC）并不能确定明确的诊断。本试验性研究旨在探讨经液基细胞学（LBC）处理的尿液中是否存在成纤维细胞生长因子受体 3（FGFR3）和端粒酶逆转录酶（TERT）基因突变，这是否能提高细胞学的诊断性能，尤其是在确定 AUC 和 SHGUC 的不确定类别时：方法：对 82 名患有原发性肿瘤或正在接受监测的 UC 患者和 10 名健康人的尿液样本进行了检查。采用薄层预处理法（THIN PREP）进行细胞学检查，然后从尿液沉淀物中分离 DNA。利用 PCR 和 Sanger 测序法对 70 例患者（63 例患者和 7 例对照）的 FGFR3 基因第 7 和第 10 外显子以及 TERT 基因启动子（pTERT）进行了靶向分子分析。分子检测结果与 TPS 细胞学分类相关，并通过膀胱镜检查的组织病理学结果进行验证：结果：在健康受试者中，细胞学检查未发现高级别尿路上皮癌（NHGUC），也未发现突变。除了一例膀胱镜检查结果不明确的病例携带 pTERT 突变外，NHGUC 细胞学检查的患者均未发现突变。在组织学确诊为 UC 的高级别尿路上皮癌细胞学病例（HGUC）（15/20，75%）中，分子分析显示存在 pTERT，但未发现 FGFR3 突变。在SHGUC和AUC细胞学检查中，经组织学确诊的UC病例中分别有3/4（75%）和4/4（100%）例检测到FGFR3和/或pTERT突变。细胞学敏感性为85.7%，细胞学-分子联合检测的敏感性提高到100%，而特异性保持不变，仍为86.3%：这项试点研究表明，在尿液LBC中加入FGFR3/pTERT分子检测可通过诊断细胞学不确定类别的BUC来提高细胞学的诊断价值。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Cytologica 生物-病理学

CiteScore

3.70

自引率

11.10%

发文量

审稿时长

4-8 weeks

期刊介绍： With articles offering an excellent balance between clinical cytology and cytopathology, ''Acta Cytologica'' fosters the understanding of the pathogenetic mechanisms behind cytomorphology and thus facilitates the translation of frontline research into clinical practice. As the official journal of the International Academy of Cytology and affiliated to over 50 national cytology societies around the world, ''Acta Cytologica'' evaluates new and existing diagnostic applications of scientific advances as well as their clinical correlations. Original papers, review articles, meta-analyses, novel insights from clinical practice, and letters to the editor cover topics from diagnostic cytopathology, gynecologic and non-gynecologic cytopathology to fine needle aspiration, molecular techniques and their diagnostic applications. As the perfect reference for practical use, ''Acta Cytologica'' addresses a multidisciplinary audience practicing clinical cytopathology, cell biology, oncology, interventional radiology, otorhinolaryngology, gastroenterology, urology, pulmonology and preventive medicine.