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Renal cell carcinoma (RCC), the most common type of kidney cancer, is increasing in incidence and is the most lethal genitourinary cancer. Due to the increasing use of abdominal imaging, incidentally detected, asymptomatic small renal masses (SRMs), most of which are RCC, have become the most common presentation of kidney cancer. Most RCC SRMs initially grow slowly or not at all, but others progress to advanced and metastatic cancer. Several diagnostic and prognostic genomic, transcriptomic and proteomic studies have been completed in RCC, however signatures for SRM progression have not been identified. In the absence of useful factors to distinguish those tumors requiring treatment for progression from those that can be managed by active surveillance alone, most SRMs are treated as RCC with surgery. Currently, the only prognostic factor at diagnosis is tumor size. Tumor growth rate also appears to identify potential progressive tumours. Identifying signatures for progression and the utilization of needle biopsies will be important for SRM patients and will guide therapy.

The use of needle biopsies in basic research is increasing, and our study provides a comprehensive analysis of their adequacy in genomic and proteomic studies of kidney cancer. Frozen clear cell renal cell carcinoma (ccRCC) needle core biopsies and sections from core biopsies embedded in optimal cutting temperature (OCT) compound were used to extract DNA, RNA and protein. Their integrity was determined using genomic and proteomic analyses. VHL mutation testing was performed on ccRCC biopsies and corresponding tumors using bulk and laser capture microdissection (LCM) extractions for comparison. Adequate amounts of good quality DNA (5.8-13.3 μg/whole core, 0.6-2.7 μg/20 sections), RNA (2.9-11.9 μg/whole core, 0.5-1.3 μg/20 sections) and protein (137.4-444 μg/whole core, 39.9-74.1 μg/20 sections) were obtained from whole core and frozen sections of ccRCC needle biopsies, respectively. We observed VHL sequence mutations in 75% of ccRCC tumors and, in most cases, the same mutations were detected in both tumors and corresponding biopsies. Mutations observed by bulk extractions from tumors and biopsies were also detected by LCM without significant differences between both methodologies. ccRCC needle biopsies provide ample material for genomic and proteomic studies of kidney cancer. They are good representatives of their corresponding tumors for VHL mutation detection using both bulk and LCM extractions. LCM does not increase sensitivity of VHL mutation detection., (Copyright © 2011 Elsevier GmbH. All rights reserved.)

A high expression level of the beta-actin protein is required for important biological mechanisms, such as maintaining cell shape, growth, and motility. Although the elevated cellular level of the beta-actin protein is directly linked to the long half-life of its mRNA, the molecular mechanisms responsible for this effect are unknown. Here we show that the RNA-binding protein HuR stabilizes the beta-actin mRNA by associating with a uridine-rich element within its 3' untranslated region. Using RNA interference to knock down the expression of HuR in HeLa cells, we demonstrate that HuR plays an important role in the stabilization but not in the nuclear/cytoplasmic distribution of the beta-actin mRNA. HuR depletion in HeLa cells alters key beta-actin-based cytoskeleton functions, such as cell adhesion, migration, and invasion, and these defects correlate with a loss of the actin stress fiber network. Together our data establish that the posttranscriptional event involving HuR-mediated beta-actin mRNA stabilization could be a part of the regulatory mechanisms responsible for maintaining cell integrity, which is a prerequisite for avoiding transformation and tumor formation.