MicroRNAs: exploring a new dimension in the pathogenesis of kidney cancer

Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. The role of the von-Hippel-Lindeau (VHL) tumour suppressor gene is well established in RCC with a loss of VHL protein leading to accumulated hypoxia-induced factor (HIF) and the subsequent transcriptional activation of multiple downstream targets. Recently, microRNAs (miRNAs) have been shown to be differentially expressed in RCC and their role in RCC pathogenesis is emerging. This month, in BMC Medicine, Gleadle and colleagues show that certain miRNAs are regulated by VHL in either a hypoxia-inducible factor (HIF)-dependent or HIF-independent manner in RCC. They also show that miRNA expression correlates with the survival of RCC patients

What can molecular pathology contribute to the management of renal cell carcinoma?

The incidence of renal cell carcinoma (RCC) is increasing and outcomes remain poor. One-third of patients with localized disease will relapse, and 5-year survival for patients with metastatic disease is less than 10%. No molecular test is currently available to identify which patients who have undergone 'curative' surgery will relapse, and which patients will respond to targeted therapy. Some well characterized biochemical pathways, such as those associated with von Hippel-Lindau disease, are aberrantly regulated in RCC and are associated with histological subtype, but the understanding of these pathways contributes little to the clinical management of patients with RCC. Gene expression and sequencing studies have increased our understanding of the genetic basis of the disease but have failed to establish any unified classification to improve molecular stratification or to predict which patients are likely to relapse or respond to targeted therapy. Instead, they have served to highlight that RCC is heterogeneous at histological, morphological, and molecular levels, and that novel approaches are required to resolve the complexity of RCC prognostication and prediction of treatment response.</p