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Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy
Keishiro Fukumoto, Shigeaki Kanatani, Georg Jaremko, Zoe West, Yue Li, Kimiharu Takamatsu, Ibrahim Al Rayyes, Shuji Mikami, Naoya Niwa, Tomas Andri Axelsson, Nobuyuki Tanaka, Mototsugu Oya, Ayako Miyakawa, Marianne Brehmer, Per Uhlén
Keishiro Fukumoto, Shigeaki Kanatani, Georg Jaremko, Zoe West, Yue Li, Kimiharu Takamatsu, Ibrahim Al Rayyes, Shuji Mikami, Naoya Niwa, Tomas Andri Axelsson, Nobuyuki Tanaka, Mototsugu Oya, Ayako Miyakawa, Marianne Brehmer, Per Uhlén
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Research Article Oncology

Three-dimensional imaging of upper tract urothelial carcinoma improves diagnostic yield and accuracy

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Abstract

Upper tract urothelial carcinoma (UTUC) is a rare form of urothelial cancer with a high incidence of recurrence and a low survival rate. Almost two-thirds of UTUCs are invasive at the time of diagnosis; therefore, improving diagnostic methods is key to increasing survival rates. Histopathological analysis of UTUC is essential for diagnosis and typically requires endoscopy biopsy, tissue sectioning, and labeling. However, endoscopy biopsies are minute, and it is challenging to cut into thin sections for conventional histopathology; this complicates diagnosis. Here, we used volumetric 3-dimensional (3D) imaging to explore the inner landscape of clinical UTUC biopsies, without sectioning, revealing that 3D analysis of phosphorylated ribosomal protein S6 (pS6) could predict tumor grade and prognosis with improved accuracy. By visualizing the tumor vasculature, we discovered that pS6+ cells were localized near blood vessels at significantly higher levels in high-grade tumors than in low-grade tumors. Furthermore, the clustering of pS6+ cells was associated with shorter relapse-free survival. Our results demonstrate that 3D volume imaging of the structural niches of pS6 cells deep inside the UTUC samples improved diagnostic yield, grading, and prognosis prediction.

Authors

Keishiro Fukumoto, Shigeaki Kanatani, Georg Jaremko, Zoe West, Yue Li, Kimiharu Takamatsu, Ibrahim Al Rayyes, Shuji Mikami, Naoya Niwa, Tomas Andri Axelsson, Nobuyuki Tanaka, Mototsugu Oya, Ayako Miyakawa, Marianne Brehmer, Per Uhlén

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Figure 6

Relapse-free survival analysis in patients with UTUC who underwent focal therapy.

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Relapse-free survival analysis in patients with UTUC who underwent focal...
Kaplan-Meier plots of relapse-free survival in patients with UTUC (n = 9) who underwent focal therapy. (A–D) Stratification of UTUC, based on 2D-analysis, into high versus low pS6+ cell ratio (A, P = 0.806) and CD34+ cell density (B, P = 0.670), and, based on 3D-analysis, into high versus low clustered pS6+ cell ratio (C, P = 0.022) and pS6+ cell density around CD34+ vessel (D, P = 0.003). Statistical analysis was performed using log–rank tests.

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