First published online as a Review in Advance on October 7, 2008Molecular Pathogenesis and Diagnostics of Bladder Cancer
Anirban P. Mitra1 and Richard J. Cote1,21Departments of Pathology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033; email:
amitra@usc.edu 2Departments of Urology, Keck School of Medicine and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California 90033; email:
cote_r@ccnt.usc.edu Despite elaborate characterization of the risk factors, bladder cancer is still a major epidemiological problem whose incidence continues to rise each year. Urothelial carcinoma is now recognized as a disease of alterations in several cellular processes. The more prevalent, less aggressive, recurrent, noninvasive tumors are characterized by constitutive activation of the Ras-MAPK pathway. The less common but more aggressive invasive tumors, which have a higher mortality rate, are characterized by alterations in the p53 and retinoblastoma pathways. Several diagnostic tests have attempted to identify these molecular alterations in tumor cells exfoliated in the urine, whereas prognostic tests have tried to identify aberrations so as to predict tumor behavior and identify therapeutic targets. The future of bladder cancer patient management will rely on the use of molecular tests to reliably diagnose the presence of disease, predict individual tumor behavior, and suggest potential targeted therapeutics.
Acronyms and Definitions
CDKI: cyclin-dependent kinase inhibitor
ECM: extracellular matrix
ELISA: enzyme-linked immunosorbent assay
FGFR: fibroblast growth factor receptor
Loss of heterozygosity: loss of an allele from a heterozygous cell locus; can result in tumor-suppressor-gene inactivation if the other allele is mutated
MAPK: mitogen-activated protein kinase
Microvessel density (MVD): mean number of vessels over a number of randomly selected areas or in the densest areas of neovascularization (known as hot spots)
MMP: matrix metalloproteinase
Relative risk: ratio of the risk of disease among the exposed population to the risk among the unexposed
Single nucleotide polymorphism (SNP): genomic DNA sequence variation due to differences in a single nucleotide; present in >1% of the population
UC: urothelial carcinoma
VEGF: vascular endothelial growth factor