Immunohistochemical biomarkers for bladder cancer prognosis

Urothelial carcinoma of the bladder (UCB) is an especially complex and heterogeneous disease with a broad spectrum of histologic findings and potentially lethal behavior. Despite advances in surgical techniques, as well as intravesical and systemic therapies, up to 30% of patients with non-muscle-invasive UCB and 50% of patients with muscle-invasive UCB experience disease progression, recurrence, and eventual death. Standard prognostic features, such as pathologic stage and grade, have limited ability to predict the outcomes of this heterogeneous population. Current risk-stratification algorithms using clinical and pathologic parameters are limited in their prognostic ability. Molecular medicine holds the promise that clinical outcomes will be improved by more accurate prognostication and directing therapy towards the mechanisms and targets associated with the growth of an individual patient's tumor. Immunohistochemical analysis of biomarker expression has provided insight into the molecular pathogenesis of UCB and offers the potential for improving clinical decision making. Numerous candidate immunohistochemical biomarkers for patients with UCB have been identified, with those relating to the cell cycle and apoptosis/cell proliferation being the most extensively studied. The present review discusses the most promising immunohistochemical biomarkers. Special attention is paid to recent data from a multi-institutional collaboration that has implemented a regulated, phased biomarker discovery and validation pathway. Because UCB tumorigenesis and progression is a process involving multiple genetic and epigenetic alterations, multiple biomarkers need to be integrated into a prognostic signature to accurately predict outcomes. There is no doubt that biomarkers will eventually guide our clinical decision making regarding follow-up scheduling and treatment choice.