Abstract

BackgroundUrothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter, or renal pelvis. Although tumors arising in these various locations have similar morphology, it is unclear whether the gene expression profiles are similar between the upper-tract (ureter and renal pelvis) and lower-tract (bladder and urethra) carcinomas. Because differences may facilitate different screening and treatment modalities, we sought to examine the relationship between urothelial carcinoma of the renal pelvis (rUC) and urothelial carcinoma of the bladder (bUC).MethodsFresh tumor tissue was collected from patients with bUC (n = 10) and benign mucosa from the bladder of individuals undergoing resection for non-UC conditions (n = 7). Gene expression profiles from these samples were determined using high-throughput Affymetrix gene expression microarray chips. Bioinformatic approaches were used to compare the gene expression profiles of these samples with those of rUC samples and normal kidney samples that had been described previously.ResultsUsing unsupervised analytic approaches, rUC and bUC were indistinguishable. Yet when a supervised analytic approach was used, a small number of differentially expressed genes were identified; these differences were most likely limited to a single pathway--the chloride ion binding activity pathway--which was more frequently activated in rUC than in bUC.ConclusionsWe found that the gene expression profiles of UCs from the upper and lower tract were extremely similar, suggesting that similar pathogenic mechanisms likely function in the development of these tumors. The differential expression of genes in the identified pathway may represent a new avenue for detection of upper-tract tumors.

Highlights

  • Urothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter, or renal pelvis

  • Genes that map to regions of chromosome amplification typically produce more RNA than is found in cytogenetically normal samples; likewise, genes that map to regions of chromosome deletion typically produce less RNA

  • We scanned the gene expression data to determine if UCs isolated from the renal pelvis showed a different spectrum of chromosomal abnormalities than UCs isolated from the bladder

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Summary

Introduction

Urothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter, or renal pelvis. Tumors arising in these various locations have similar morphology, it is unclear whether the gene expression profiles are similar between the upper-tract (ureter and renal pelvis) and lower-tract (bladder and urethra) carcinomas. In order to address this, we collected samples from patients with lower-tract UC (bladder; bUC) and benign mucosa samples from bladder of individuals undergoing resection for non-UC conditions; their gene expression profiles were obtained using Affymetrix gene expression profile arrays. These profiles were compared with profiles from upper-tract UC (renal pelvis; rUC) and benign renal pelvic mucosa (rNO). This is the first report to compare the gene expression profiles of UCs of the upper and lower tracts

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