Clinical feasibility of a modified urinary cytology framework with targeted next-generation sequencing analysis
Related Experiment Video
Updated: Nov 5, 2026
Integration of Wet and Dry Bench Processes Optimizes Targeted Next-generation Sequencing of Low-quality and Low-quantity Tumor Biopsies
Published on: April 11, 2016
Ibu Matsuzaki1, Yuichi Kinoshita2, Hirokazu Nagai3
1Department of Human Pathology, Wakayama Medical University, Wakayama, Japan.
Introduction:
The Paris System (TPS) for urinary cytology focuses primarily on high-grade urothelial carcinoma (HGUC) and has limited utility for low-grade UC. To address this limitation, we evaluated a modified framework, the Wakayama Urinary Cytology System (WUCS), which incorporates a new diagnostic category, "Atypical Urothelial Cells of Unknown Significance" (AUC-US). We investigated the clinical feasibility of this modified framework using clinicopathological findings and targeted next-generation sequencing (NGS).
Materials And Methods:
We retrospectively reviewed 2012 urinary cytology specimens from 1159 patients. WUCS subdivided the TPS category "negative for HGUC" by introducing AUC-US and stratified specimens into 5 categories. AUC-cannot exclude HGUC corresponded to AUC in TPS. Targeted NGS analysis of 8 UC-related genes was performed on 85 specimens from 64 patients selected according to predefined technical and clinical criteria.
Results:
WUCS classified 74.9% of cases as negative for malignancy, 9.0% as AUC-US, 9.0% as AUC-cannot exclude HGUC, 2.6% as suspicious for malignancy, and 4.3% as malignancy. Notably, 9.3% of HGUC cases were reclassified as AUC-US rather than negative for HGUC, and 30.9% of low-grade UC cases were identified within the AUC-US category. Targeted NGS analyses suggested the presence of genetic alterations in a subset of AUC-US specimens.
Conclusions:
These findings suggest that the modified framework, supported in part by targeted NGS analysis, may complement TPS by facilitating risk stratification of mildly atypical urinary specimens. However, further prospective multicenter studies are needed to assess its reproducibility and clinical utility.
