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Are urothelial carcinomas of the upper urinary tract a distinct entity from urothelial carcinomas of the urinary bladder? Behavior of urothelial carcinoma after radical surgery with respect to anatomical location: a case control study.

ABSTRACT: To compare the prognosis of upper urinary tract (UUT)-urothelial carcinoma (UC) and UC of the bladder (UCB) by pathological staging in patients treated with radical surgeries.The study population comprised 335 and 302 consecutive radical surgery cases performed between 1991 and 2010 for UUT-UC and UCB, respectively. Five-year recurrence-free survival (RFS) and cancer-specific survival (CSS) rates were analyzed. The median follow-up period of all subjects was 59.3 months (range, 0.1-261.0 months).No difference was observed in median patient age, distribution of pathologic T stage, or rates of positive surgical margin between the two groups. The UUT-UC group had significantly more frequent hydronephrosis than the USB group (48.1% vs. 20.2%, p?

SUBMITTER: Kim M

PROVIDER: S-EPMC4369352 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Are urothelial carcinomas of the upper urinary tract a distinct entity from urothelial carcinomas of the urinary bladder? Behavior of urothelial carcinoma after radical surgery with respect to anatomical location: a case control study.

Kim Myong M Jeong Chang Wook CW Kwak Cheol C Kim Hyeon Hoe HH Ku Ja Hyeon JH

BMC cancer 20150318

<h4>Background</h4>To compare the prognosis of upper urinary tract (UUT)-urothelial carcinoma (UC) and UC of the bladder (UCB) by pathological staging in patients treated with radical surgeries.<h4>Methods</h4>The study population comprised 335 and 302 consecutive radical surgery cases performed between 1991 and 2010 for UUT-UC and UCB, respectively. Five-year recurrence-free survival (RFS) and cancer-specific survival (CSS) rates were analyzed. The median follow-up period of all subjects was 59 ...[more]

PMID: 25886012

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Project description:BACKGROUND AND AIMS:Oncogenesis is a multistep process, resulting from the accumulations of multiple mutations. Of these mutations, self-sufficiency in growth signals, i.e., disruption of cell growth regulation, is the first episode. Nonetheless, the genes associated with cell growth dysregulation have seldom been systematically evaluated in either urothelial carcinomas of upper urinary tract (UTUC) or urothelial carcinomas of urinary baldder (UBUC). By data mining a published transcriptomic dataset of UBUCs (GSE31684), we identified the NDN gene as one of the most significant of those associated with the regulation of cell growth and found this gene is associated with advanced tumor status and metastatic disease (GO:0001558). Accordingly, we analyzed NDN transcript and protein expression with their clinicopathological significance. MATERIALS AND METHODS:We used real time RT-PCR to detect NDN transcript levels in 27 UTUCs and 27 UBUCs, respectively. Immunohistochemical study was performed to determine NDN protein (a.k.a. Necdin) expression evaluated by H-score method in 340 UTUCs and 295 UBUCs. NDN expression was further correlated with clinicopathological features and disease-specific survival (DSS) and metastasis-free survival (MeFS). RESULTS:NDN transcriptional level was significantly higher in UCs of both sites with stepwise more advanced pT statuses. Through immunohistochemistry, we found NDN protein expression was significantly associated with adverse clinicopathological parameters, e.g., advanced pT status, nodal metastasis, high grade histological patterns, and frequent mitotses (all P<0.05). In univariate analysis, NDN overexpression not only predicted worse DSS and MeFS in both the UTUC and UBUC groups, it also served as an independent prognostic factor for DSS and MeFS in multivariate analysis (all P<0.05). CONCLUSIONS:NDN may play an important role in tumor progression in UC and could serve as a prognostic biomarker and a potential novel therapeutic target in UC.

Project description:Recurrent upper tract urothelial carcinomas (UTUCs) arise in the context of nephropathy linked to exposure to the herbal carcinogen aristolochic acid (AA). Here we delineated the molecular programs underlying UTUC tumorigenesis in patients from endemic aristolochic acid nephropathy (AAN) regions in Southern Europe. We applied an integrative multiomics analysis of UTUCs, corresponding unaffected tissues and of patient urines. Quantitative microRNA (miRNA) and messenger ribonucleic acid (mRNA) expression profiling, immunohistochemical analysis by tissue microarrays and exome and transcriptome sequencing were performed in UTUC and nontumor tissues. Urinary miRNAs of cases undergoing surgery were profiled before and after tumor resection. Ribonucleic acid (RNA) and protein levels were analyzed using appropriate statistical tests and trend assessment. Dedicated bioinformatic tools were used for analysis of pathways, mutational signatures and result visualization. The results delineate UTUC-specific miRNA:mRNA networks comprising 89 miRNAs associated with 1,862 target mRNAs, involving deregulation of cell cycle, deoxyribonucleic acid (DNA) damage response, DNA repair, bladder cancer, oncogenes, tumor suppressors, chromatin structure regulators and developmental signaling pathways. Key UTUC-specific transcripts were confirmed at the protein level. Exome and transcriptome sequencing of UTUCs revealed AA-specific mutational signature SBS22, with 68% to 76% AA-specific, deleterious mutations propagated at the transcript level, a possible basis for neoantigen formation and immunotherapy targeting. We next identified a signature of UTUC-specific miRNAs consistently more abundant in the patients' urine prior to tumor resection, thereby defining biomarkers of tumor presence. The complex gene regulation programs of AAN-associated UTUC tumors involve regulatory miRNAs prospectively applicable to noninvasive urine-based screening of AAN patients for cancer presence and recurrence.

Dataset Information

Are urothelial carcinomas of the upper urinary tract a distinct entity from urothelial carcinomas of the urinary bladder? Behavior of urothelial carcinoma after radical surgery with respect to anatomical location: a case control study.

Publications

Are urothelial carcinomas of the upper urinary tract a distinct entity from urothelial carcinomas of the urinary bladder? Behavior of urothelial carcinoma after radical surgery with respect to anatomical location: a case control study.

Similar Datasets

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