Emerging evidence shows that microRNAs (miR) are involved in the pathogenesis of a variety of cancers, including prostate carcinoma (PCa). Little information is available regarding miR expression levels in lymph node metastasis of prostate cancer or the potential of miRs as prognostic markers in this disease. Therefore, we analyzed the global expression of miRs in benign, hyperplastic prostate tissue (BPH), primary PCa of a high risk group of PCa patients, and corresponding metastatic tissues by microarray analysis. Consistent with the proposal that some miRs are oncomirs, we found aberrant expression of several miRs, including the downregulation of miR-221, in PCa metastasis. Downregulation of miR-221 was negatively correlated with the expression of the proto-oncogen c-kit in primary carcinoma. In a large study cohort, the prostate-specific oncomir miR-221 was progressively downregulated in aggressive forms of PCa. Downregulation of miR-221 was associated with clinicopathological parameters, including the Gleason score and the clinical recurrence during follow up. Kaplan-Meier estimates and Cox proportional hazard models showed that miR-221 downregulation was linked to tumor progression and recurrence in a high risk prostate cancer cohort. Our results showed that progressive miR-221 downregulation hallmarks metastasis and presents a novel prognostic marker in high risk PCa. This suggests that miR-221 has potential as a diagnostic marker and therapeutic target in PCa.Prostate cancer is one of the most common visceral malignant neoplasms in men. It was estimated in 2006 that 345,000 cases were newly diagnosed in the European community.1 The natural history of prostate carcinoma (PCa) varies from an indolent disease that might not cause symptoms during a patient's lifetime to a highly aggressive cancer that metastasises quickly and causes severe pain and untimely death. The marked disparity between these biological behaviors is not currently understood and had an increasing socioeconomic impact. Over the years, several potential prognostic markers for PCa, including mRNA based gene expression signatures, have been identified.2-4 Unfortunately, both clinical criteria and molecular genetics approaches have had only limited success in patient stratification.While low risk patients rarely develop tumor progression or clinical recurrence after radical prostatectomy, patients with high risk PCa had a 50% risk of progression at 5 years. 5Moreover we could show recently in a multicenter study on more than 800 high risk PCa patients that 63% of the patients experienced 15-years metastasis free survival after radical prostatectomy (unpublished data). The main known prognostic factors for treatment efficacy and survival, the PSA-value at diagnosis and the Gleason score, 1,6,7 were not useful in this high risk cohort as predictor for clinical progression and mortality. Therefore new prognostic markers for high and low risk PCa patients are urgently needed to optimize and to individualize therapy strategies.MicroRNAs (miR) are...

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