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Validation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Study

2019Journal article Open access
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dc.contributor.authorBatista, Rui
dc.contributor.authorVinagre, João
dc.contributor.authorPrazeres, Hugo
dc.contributor.authorSampaio, Cristina
dc.contributor.authorPeralta, Pedro
dc.contributor.authorConceição, Paulo
dc.contributor.authorSismeiro, Amílcar
dc.contributor.authorLeão, Ricardo
dc.contributor.authorGomes, Andreia
dc.contributor.authorFurriel, Frederico
dc.contributor.authorOliveira, Carlos
dc.contributor.authorTorres, João Nuno
dc.contributor.authorEufrásio, Pedro
dc.contributor.authorAzinhais, Paulo
dc.contributor.authorAlmeida, Fábio
dc.contributor.authorGonzalez, Edwin Romero
dc.contributor.authorBidovanets, Bohdan
dc.contributor.authorEcke, Thorsten
dc.contributor.authorStinjs, Pascal
dc.contributor.authorPascual, Álvaro Serrano
dc.contributor.authorAbdelmalek, Rabehi
dc.contributor.authorVillafruela, Ainara
dc.contributor.authorBeardo-Villar, Pastora
dc.contributor.authorFidalgo, Nuno
dc.contributor.authorÖztürk, Hakan
dc.contributor.authorGonzalez-Enguita, Carmen
dc.contributor.authorMonzo, Juan
dc.contributor.authorLopes, Tomé
dc.contributor.authorÁlvarez-Maestro, Mario
dc.contributor.authorServan, Patricia Parra
dc.contributor.authorDe La Cruz, Santiago Moreno Perez
dc.contributor.authorPerez, Mario Pual Sanchez
dc.contributor.authorMáximo, Valdemar
dc.contributor.authorSoares, Paula
dc.date.accessioned2020-03-15T18:15:39Z
dc.date.available2020-03-15T18:15:39Z
dc.date.issued2019
dc.description.abstractBladder cancer (BC), the most frequent malignancy of the urinary system, is ranked the sixth most prevalent cancer worldwide. Of all newly diagnosed patients with BC, 70-75% will present disease confined to the mucosa or submucosa, the non-muscle-invasive BC (NMIBC) subtype. Of those, approximately 70% will recur after transurethral resection (TUR). Due to high rate of recurrence, patients are submitted to an intensive follow-up program maintained throughout many years, or even throughout life, resulting in an expensive follow-up, with cystoscopy being the most cost-effective procedure for NMIBC screening. Currently, the gold standard procedure for detection and follow-up of NMIBC is based on the association of cystoscopy and urine cytology. As cystoscopy is a very invasive approach, over the years, many different noninvasive assays (both based in serum and urine samples) have been developed in order to search genetic and protein alterations related to the development, progression, and recurrence of BC. TERT promoter mutations and FGFR3 hotspot mutations are the most frequent somatic alterations in BC and constitute the most reliable biomarkers for BC. Based on these, we developed an ultra-sensitive, urine-based assay called Uromonitor®, capable of detecting trace amounts of TERT promoter (c.1-124C > T and c.1-146C > T) and FGFR3 (p.R248C and p.S249C) hotspot mutations, in tumor cells exfoliated to urine samples. Cells present in urine were concentrated by the filtration of urine through filters where tumor cells are trapped and stored until analysis, presenting long-term stability. Detection of the alterations was achieved through a custom-made, robust, and highly sensitive multiplex competitive allele-specific discrimination PCR allowing clear interpretation of results. In this study, we validate a test for NMIBC recurrence detection, using for technical validation a total of 331 urine samples and 41 formalin-fixed paraffin-embedded tissues of the primary tumor and recurrence lesions from a large cluster of urology centers. In the clinical validation, we used 185 samples to assess sensitivity/specificity in the detection of NMIBC recurrence vs. cystoscopy/cytology and in a smaller cohort its potential as a primary diagnostic tool for NMIBC. Our results show this test to be highly sensitive (73.5%) and specific (93.2%) in detecting recurrence of BC in patients under surveillance of NMIBC.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationFront Genet. 2019 Dec 18;10:1237.pt_PT
dc.identifier.doi10.3389/fgene.2019.01237pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.26/31737
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.subjectUrinary Bladder Neoplasmspt_PT
dc.subjectBiomarkers, Tumorpt_PT
dc.subjectNeoplasias da Bexiga Urináriapt_PT
dc.subjectBiomarcadores Tumoraispt_PT
dc.titleValidation of a Novel, Sensitive, and Specific Urine-Based Test for Recurrence Surveillance of Patients With Non-Muscle-Invasive Bladder Cancer in a Comprehensive Multicenter Studypt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage1237pt_PT
oaire.citation.titleFrontiers in geneticspt_PT
oaire.citation.volume10pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

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