4%, compared to 63. 0% in models excluding EZH2 expression. Discussion The present study defines EZH2 as a powerful and inde pendent negative prognostic marker of CSS in patients with metastasized small molecule and non metastasized RCC. Thus, assessment of EZH2 expression may allow improved patient selection for systemic therapies. Moreover, inte gration of the EZH2 status into current prognostic mod els could result in more accurate survival prediction and may also be useful for individualizing Inhibitors,Modulators,Libraries follow up and selecting patients for clinical trials. RCC is commonly characterized by a poor response towards current treatment options. Even after complete resection of the primary tumor, relapse occurs in 20 30% of cases. The overall 5 year survival rate is 60%.

in patients with metastases, the median survival is only about 13 months, with a 5 year survival of less than 10%. Cytokine therapy and novel targeted thera pies, i. e. tyrosine kinase inhibitors, have been of limited Inhibitors,Modulators,Libraries benefit. Progression and treatment response of the disease are still not sufficiently predictable. Suita ble molecular markers could help to refine individual risk stratification and treatment plans. However, for RCC, as for other cancers in general, only few markers have been validated for clinical practice. This may be partly due to the fact that many studies have been small and poorly designed, used inappropriate statistical analy sis, and employed different assay methods and outcome measures. The present study, defining EZH2 as a novel prognos tic marker in RCC, has been conducted according to the REMARK criteria.

These include a large sample size, a long prospective follow up of patients, and a description of the predictive value of the marker. Possi ble limitations of our study include the lack of external validation using Inhibitors,Modulators,Libraries a second cohort of patients with RCC. For analyzing RCC patients without metastases, our Cox regression model Inhibitors,Modulators,Libraries which included tumor stage, grading, Karnofsky performance index, age, sex, histopathological subtype, and EZH2 expression revealed a concordance probability of 73. 4% compared to 71. 8% excluding EZH2 expression. In RCC patients with metastatic disease, the concordance probability including EZH2 expression was 68. 4%, compared to 63. 0% excluding EZH2 expression.

These values are in a similar range as obtained by the University of California Los Angeles Integrated Staging System, a well accepted prognostic factor model for RCC with good predictive accuracy, which Inhibitors,Modulators,Libraries exhibits a concordance index of 76%. Including molecular markers to the clinical models increased the concordance probability, in our model as well as in the UISS model. Therefore, EZH2 should represent a powerful new marker for predicting prognosis in RCC and could be integrated in established prognostic mod els to provide an even better consultation for patients regarding diagnosis, selleck inhibitor treatment, and follow up.