Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma (Lynch Syndrome...)

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 Molecular Analysis of Upper Tract and Bladder Urothelial Carcinoma: Results from a Microarray Comparison

 ....Furthermore, there are specific environmental exposures and hereditary syndromes associated with an increased risk of development of UTUC. Patients with Hereditary Nonpolyposis Colorectal Cancer have a defect in DNA repair genes resulting in a hypermutable state. These patients are known to have a 22 fold increased risk of developing UTUC [27].... 

..... This study has a number of limitations. First, the numbers are small given the rarity of the disease. Second, this study was conducted using publically available data and there was no central review of the pathology. Despite these limitations, we believe this is the first study of gene expression comparing UTUC and UCB to find specific examples that upper tract tumors may represent a unique sub-population of urothelial carcinoma.

 Conclusion
By separating upper tract urothelial carcinoma and bladder urothelial carcinoma by T stage in our analysis of microarray data, we were able to detect molecular differences in UTUC when compared to UCB. Differentially expressed genes have immunogenic functions, and were involved in the TNF and HFG pathways. Upper tract tumors tend to over-express luminal genes. One gene highly over-expressed in upper tract urothelial carcinoma, SLITRK6, is the target of an antibody-drug conjugate currently being evaluated in phase I clinical trials.