The urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carcinoma are bladder carcinomas, and urothelial carcinomas of the renal pelvis and ureter account for only approximately 7% of the total. Urothelial tumours arise and evolve through divergent phenotypic pathways. Some tumours progress from urothelial hyperplasia to low-grade non-invasive superficial papillary tumours. More aggressive variants arise either from flat, high-grade carcinoma in situ (CIS) and progress to invasive tumours, or they arise de novo as invasive tumours. Low-grade papillary tumors frequently show a constitutive activation of the receptor tyrosine kinase-Ras pathway, exhibiting activating mutations in the HRAS and fibroblast growth factor receptor 3 (FGFR3) genes. In contrast, CIS and invasive tumors frequently show alterations in the TP53 and RB genes and pathways. Invasion and metastases are promoted by several factors that alter the tumour microenvironment, including the aberrant expression of E-cadherins (E-cad), matrix metalloproteinases (MMPs), angiogenic factors such as vascular endothelial growth factor (VEGF).

Human Diseases; Cancer: specific types
BRITE hierarchy

Nannospalax galili (Upper Galilee mountains blind mole rat) [GN:ngi]

PMID:17158541

Mitra AP, Datar RH, Cote RJ.

Molecular pathways in invasive bladder cancer: new insights into mechanisms, progression, and target identification.

J Clin Oncol 24:5552-64 (2006)
DOI:10.1200/JCO.2006.08.2073

PMID:16474624

Wolff EM, Liang G, Jones PA.

Mechanisms of Disease: genetic and epigenetic alterations that drive bladder cancer.

Nat Clin Pract Urol 2:502-10 (2005)
DOI:10.1038/ncpuro0318

PMID:16110317

Wu XR.

Urothelial tumorigenesis: a tale of divergent pathways.

Nat Rev Cancer 5:713-25 (2005)
DOI:10.1038/nrc1697

PMID:11103787

Brown NS, Jones A, Fujiyama C, Harris AL, Bicknell R.

Thymidine phosphorylase induces carcinoma cell oxidative stress and promotes secretion of angiogenic factors.

Cancer Res 60:6298-302 (2000)

PMID:12850530

Bellmunt J, Hussain M, Dinney CP.

Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family.

Crit Rev Oncol Hematol 46 Suppl:S85-104 (2003)
DOI:10.1016/S1040-8428(03)00067-2

PMID:17149381

Sugano K, Kakizoe T.

Genetic alterations in bladder cancer and their clinical applications in molecular tumor staging.

Nat Clin Pract Urol 3:642-52 (2006)
DOI:10.1038/ncpuro0649

PMID:15746962

Dunn KL, Espino PS, Drobic B, He S, Davie JR.

The Ras-MAPK signal transduction pathway, cancer and chromatin remodeling.

Biochem Cell Biol 83:1-14 (2005)
DOI:10.1139/o04-121

PMID:15551095

Williams SG, Stein JP.

Molecular pathways in bladder cancer.

Urol Res 32:373-85 (2004)
DOI:10.1007/s00240-003-0345-y