Abstract 3012: Development of a microRNA signature for risk of progression in renal cell carcinoma

Abstract

Abstract The incidence of asymptomatic pathologically localized renal cell carcinoma (RCC) has shown the greatest increase in recent decades. Despite the finding of organ-confined (pT1 or T2) disease at the time of nephrectomy, a subset of patients will have local recurrence or distant metastasis after nephrectomy. Most solid neoplasms are now thought to accumulate a series of genetic and epigenetic changes as they progress through well-defined clinical and histopathological changes. The association of particular molecular markers with progression and outcome of disease means that the status of certain markers can be used to identify the presence of disease and its likelihood for progression. To identify an epigenetic signature that may predict recurrence in patients with organ-confined RCC, we examined RNA hybridized to the Agilent microRNA (miRNA) array from a large number (>100) of RCC patients with extensive clinicopathological annotation. The potential of miRNAs as biomarkers for risk of progression and early detection of recurrent RCC has not yet been studied. Since approximately 90% of metastatic RCC is of clear cell histology, we examined only this histological cell type. The cell type and grade of the RCC was re-reviewed blind by a single pathologist. miRNA expression signatures were established from a series of low grade (I-II), low stage (pT1-2) clear cell RCC with no evidence of disease after nephrectomy for at least 5 years; a series of high grade, high stage (pT3-4), clear cell RCC; and a series of low grade and low stage clear cell RCC that progressed. The expression of particular miRNAs was validated by qRT-PCR. In the growing number of patients who have undergone surgical resection for organ-confined RCC, the near term goal would be to identify those that should be followed more closely and a future goal, depending upon results of ongoing therapeutic trials, to be directed to adjuvant therapy. There would also be cost benefits in potentially following those RCC patients with lowest risk of progression less frequently. MiRNA signatures obtained by our study will address the clinical question whether risk of progression could be defined in patients with organ-confined RCC at initial surgery. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3012.