scholarly journals Comparison of Genomic Characterization in Upper Tract Urothelial Carcinoma and Urothelial Carcinoma of the Bladder

2021 ◽  
Author(s):  
Kaiwei Yang ◽  
Wei Yu ◽  
Huanhuan Liu ◽  
Feng Ding ◽  
Yanrui Zhang ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Biological Diversity ◽  
Upper Tract Urothelial Carcinoma ◽  
Driver Gene ◽  
Driver Genes ◽  
Upper Tract ◽  
Significant Difference ◽  
Genomic Characterization ◽  
Carcinoma Of The Bladder ◽  
Subclonal Mutation

Abstract Background: Different genomic characterization in urothelial carcinoma (UC) by site of origin, may imply contrasting therapeutic opportunities and pathogenetic mechanisms. The aim of this study was to investigate whether the differences between upper tract urothelial carcinoma (UTUC) and urothelial carcinoma of the bladder (UCB) result from intrinsic biological diversity.Methods: We prospectively sequenced 118 tumors and matched blood DNA from Chinese UC patients using next-generation sequencing (NGS) techniques, including 45 UTUC and 73 UCB.Results: There were marked disparities in the mutational landscape for UC according to race and site of origin. Signature 22 for exposure to aristolochic acid (AA) and signature 10 for defects in polymerase POLE were only observed in the UTUC cohort. Conversely, signature 6 for defective DNA mismatch repair only existed in the UCB cohort. Compared to UCB, UTUC had higher clonal (p<0.001) and subclonal mutation numbers (p=0.015). TP53, PIK3CA, and FGFR3 mutations may be the driver genes for UTUC, whereas for UCB, the driver gene may be BRCA1. UTUC patients had lower PD-L1 than UCB patients. There was no significant difference in the number of DDR mutations, copy number variation (CNV) counts, tumor mutational burden (TMB) or clinical actionability between UTUC and UCB.Conclusions: UTUC and UCB exhibit significant differences in the prevalence of common genomic landscape and carcinogenesis. Consequently, molecular subtypes differ according to location, and these results may have important implications for the site-specific management of patients with urothelial carcinoma. Mutational signature may be used as a screening tool to assist clinical differential diagnosis between UTUC and UCB.

Comparison of upper tract urothelial carcinoma and urothelial carcinoma of the bladder to reveal key differences in mutational profile and load.

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 4522-4522 ◽  
Author(s):  
Sumanta K. Pal ◽  
Siraj Mahamed Ali ◽  
Julia Andrea Elvin ◽  
Garrett Michael Frampton ◽  
Jo-Anne Vergilio ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Upper Tract Urothelial Carcinoma ◽  
Upper Tract ◽  
Carcinoma Of The Bladder

Correlation of MECA-79-positive high endothelial venule density with clinical outcomes in upper tract urothelial carcinoma patients treated with radical nephroureterectomy.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 417-417
Author(s):  
Yasuhiro Hashimoto ◽  
Hayato Yamamoto ◽  
Tohru Yoneyama ◽  
Atsushi Imai ◽  
Shingo Hatakeyama ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Clinical Outcomes ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Small Sample ◽  
Upper Tract Urothelial Carcinoma ◽  
Radical Nephroureterectomy ◽  
Upper Tract ◽  
Significant Difference ◽  
The Mean

417 Background: High endothelial venules (HEVs) are present in lymph nodes and tertiary lymphoid organs. It has been reported that low HEV density is associated with the poor prognosis of several carcinomas. MECA-79 antibody recognizes L-selectin ligand (6-sulfosialyl Lewis X glycan) expressed in HEV. In the present study, we examined whether MECA-79 positive HEV density was associated with clinical outcomes of patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Methods: Eighty-eight patients with UTUC who underwent RNU at the Hirosaki University hospital between January 2008 and December 2016 were enrolled. Tissue microarray for MECA-79 was performed, and HEV densities were calculated. HEV density < 1.5/mm2 was defined as HEV (−); HEV density ≥1.5/mm2 was defined as HEV(+). Results: Of 88 patients, 64 (72.7%) were male and 24 (27.2%) were female. The average age was 68.5 years (range, 36–84 years). Fifty-three patients (60.2%) had previously undergone neoadjuvant chemotherapy. The mean observation period was 39.0 months. Twenty-one (23.8%) patients developed recurrence, whereas 16 (33.3%) patients died during follow-up. Five-year cause-specific survival (CSS) rate was 66.1%, and five-year disease-free survival (DFS) rate was 70.7%. In our cohort, 25 (28.4%) patients were found to be HEV(−), whereas 63 (71.5%) were found to be HEV(+). The mean HEV density was 6.3/mm2(0-41.6). The 5-year DFS rates for HEV (+) and HEV (−) patients were 78.0% and 53.9%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.042). Moreover, the 5-year CSS rates for HEV (+) and HEV (−) patients were 72.5% and 53.4%, respectively, with a statistically significant difference between the groups. (log-rank, p = 0.0036). Conclusions: Low MECA-79-positive HEV density may be associated with poor prognosis of patients with UTUC treated with RNU. Despite the small sample size and preliminary nature of our study, our study provides valuable insights to guide future research.

MP71-01 COMPREHENSIVE GENOMIC CHARACTERIZATION OF UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

2017 ◽  
Vol 197 (4S) ◽  
Author(s):  
Tyler Moss ◽  
Yuan Qi ◽  
Bo Peng ◽  
Liu Xi ◽  
Maribel Mosqueda ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Upper Tract Urothelial Carcinoma ◽  
Upper Tract ◽  
Genomic Characterization

Prognostic role of programmed cell death protein 1 expression in surgically treated patients with upper tract urothelial carcinoma.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 402-402
Author(s):  
Nozomi Hayakawa ◽  
Eiji Kikuchi ◽  
Ryuichi Mizuno ◽  
Keishiro Fukumoto ◽  
Takeo Kosaka ◽  
...  
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Protein Expression ◽  
Urothelial Carcinoma ◽  
Lymphovascular Invasion ◽  
Upper Tract Urothelial Carcinoma ◽  
Upper Tract ◽  
Significant Difference ◽  
Cell Death Protein

402 Background: Programmed cell death protein (PD-1) expressed on active T cells, and its ligand PD-L1 expressed on the surface of cancer cells, complementarily down-regulate T cell activation and are related to immune tolerance. A close association between PD-1 expression and poor prognosis has been reported in several cancers, however, in upper tract urothelial carcinoma (UTUC) the role of PD-1 expression on clinical outcome has not been investigated. Methods: The protein expression of PD-1 was evaluated by immunohistochemistry and the relationship with clinicopathological features was investigated in surgical specimens obtained from 100 patients who had been surgically treated for UTUC. At a magnification of 200x, PD-1 protein expression was estimated and the positive cells were graded as no (negative), moderate (1-10 cells), and strong ( > 10 cells). Results: Twenty-four patients (24.0%) had strong PD-1 staining, 32 patients (32.0%) had moderate PD-1 staining, and 44 patients (44.0%) had no PD-1 staining. PD-1 staining was associated with pathological T stage (p = 0.023), tumor grade (p = 0.005), and lymphovascular invasion (p = 0.033). Lymphovascular invasion (p < 0.001) and PD-1 staining (p = 0.02) were independent factors for predicting disease metastasis. The 5-year matastatic free survival rate in patients with strong PD-1 staining was 57.3 %, which was significantly lower than that with no PD-1 staining (87.3%, p=0.001) and that with moderate PD-1 staining (74.3%, p = 0.05). In a sub-group analysis of patients with ≥pT2 (N = 59), a significant difference in disease metastasis was observed between patients with strong PD-1 staining and no PD-1 staining (p = 0.018), but was not observed between strong and moderate PD-1 staining (p = 0.146). Conclusions: PD-1 expression may be a useful indicator for a worse prognosis in UTUC patients who undergo radical nephroureterectomy. Targeting therapy against PD-1 might be a promising therapeutic modality for UTUC.

scholarly journals Comparison of Radical Nephroureterectomy and Partial Ureterectomy for the Treatment of Upper Tract Urothelial Carcinoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7
Author(s):  
Jianzhong Zhang ◽  
Feiya Yang ◽  
Mingshuai Wang ◽  
Yinong Niu ◽  
Weicheng Chen ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Kidney Function ◽  
Operation Time ◽  
Upper Tract Urothelial Carcinoma ◽  
Radical Nephroureterectomy ◽  
Cox Regression Analysis ◽  
Upper Tract ◽  
Significant Difference ◽  
The Mean ◽  
Kidney Functions

This study aimed to compare the oncological and renal outcomes of partial ureterectomy (PU) versus radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). UTUC patients’ clinical information was reviewed, and progression-free survival (PFS), overall survival (OS), and kidney function were collected. The mean follow-up period was 59 (6–135) months in the RNU group and 34.5 (5–135) months in the PU group. The mean operation time in the PU group was 141 (64–340) min, which is significantly shorter than the RNU group (P<0.01). Regarding kidney function at one year or two years after operation, the PU group had significantly improved mean estimated glomerular filtration rate (eGFR) levels and a remarkably decreased constitution of patients with chronic kidney disease (CKD) III or higher group (P<0.05). There was no significant difference in PFS and OS between the RNU group and the PU group (P>0.05). Multifactor Cox regression analysis indicated that age and the preoperative CKD stages were independent risk factors for poor kidney functions of UTUC patients. Compared to patients in RNU group, patients in PU have no significant difference in survival time but have shorter operation time, shorter hospital stay, and improved kidney functions.

Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma

2017 ◽  
Vol 72 (4) ◽  
pp. 641-649 ◽  
Author(s):  
Tyler J. Moss ◽  
Yuan Qi ◽  
Liu Xi ◽  
Bo Peng ◽  
Tae-Beom Kim ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Upper Tract Urothelial Carcinoma ◽  
Upper Tract ◽  
Genomic Characterization
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