Diagnostic value of a comprehensive, urothelial carcinoma-specific next-generation sequencing panel in urine cytology and bladder tumor specimens.

Autor: Sun T; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Hutchinson L; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Tomaszewicz K; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Caporelli ML; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Meng X; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., McCauley K; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Fischer AH; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Cosar EF; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts., Cornejo KM; Department of Pathology, UMass Memorial Medical Center, University of Massachusetts Medical School, Worcester, Massachusetts.; Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Jazyk: angličtina
Zdroj: Cancer cytopathology [Cancer Cytopathol] 2021 Jul; Vol. 129 (7), pp. 537-547. Date of Electronic Publication: 2021 Feb 04.
DOI: 10.1002/cncy.22410
Abstrakt: Background: Urine cytology can reliably diagnose high-grade urothelial carcinoma (HGUC) but not low-grade urothelial carcinoma (LGUC), and a more sensitive test is needed. Previously, a pilot study highlighted the possible diagnostic utility of next-generation sequencing (NGS) in identifying both LGUC and HGUC in urine cytology specimens.
Methods: Twenty-eight urine ThinPrep cytology specimens and preceding or subsequent bladder tumor biopsy/resection specimens obtained within 3 months were included in the study (LGUC, n = 15; HGUC, n = 13). A customized, bladder-specific NGS panel was performed; it covered 69 frequently mutated or altered genes in urothelial carcinoma (UC) that were reported by The Cancer Genome Atlas and the Catalogue of Somatic Mutations in Cancer.
Results: The sequencing results were compared between the urine cytology specimens and the corresponding bladder tumor biopsies/resections. TP53 was the most frequently identified mutation in HGUC cases (11 of 13 [85%]). PIK3CA and KDM6A were the most frequently identified mutations in LGUC: they occurred in 7 of 15 cases (47%) and in 6 of 15 cases (40%), respectively. Additional frequent mutations identified in the panel included ARID1A (n = 5), EP300 (n = 4), LRP1B (n = 3), ERBB2 (n = 2), STAG2 (n = 2), FGFR3 (n = 3), MLL (n = 2), MLL3 (n = 2), CREBBP1 (n = 1), RB1 (n = 1), and FAT4 (n = 1). Overall, the concordance between the cytology and surgical specimens was 75%. The sensitivity and specificity for identifying mutations in urine cytology specimens were 84% and 100%, respectively.
Conclusions: A bladder-specific NGS panel increases the sensitivity and specificity of urine cytology's diagnostic utility in both low- and high-grade tumors and may serve as a noninvasive surveillance method in the follow-up of patients with UC harboring known mutations.
(© 2021 American Cancer Society.)
Databáze: MEDLINE
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