Prognostic prediction in patients with metastatic renal cell carcinoma treated with sorafenib based on expression levels of potential molecular markers in radical nephrectomy specimens

Abstract

ObjectivesTo investigate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) treated with sorafenib in order to identify factors predicting susceptibility to this agent. Materials and methodsThis study included 45 consecutive patients undergoing radical nephrectomy for clear cell RCC who were diagnosed as having metastatic diseases refractory to cytokine therapy and subsequently treated with sorafenib. Expression levels of 19 molecular markers involved in the regulation of apoptosis, cell cycle, signal transduction, and angiogenesis in primary RCC specimens were measured by immunohistochemical staining. ResultsThere was no molecular marker having significant impact on the prediction of response to sorafenib. However, progression-free survival (PFS) was significantly associated with the expression levels of Bcl-xL and platelet-derived growth factor receptor (PDGFR)-α in addition to the presence of bone metastasis and C-reactive protein level on univariate analysis. Of these significant factors, PDGFR-α expression and the presence of bone metastasis appeared to be independently related to PFS by multivariate analysis. Furthermore, there were significant differences in PFS according to positive numbers of these 2 independent risk factors; that is, disease progression occurred in 2 of 7 patients who were negative for risk factor, 19 of 34 positive for a single risk factor, and 6 of 6 positive for both risk factors. ConclusionsCollectively, these findings suggest that it would be useful to consider expression levels of potential molecular markers, particularly PDGFR-α, as well as clinical parameters to select metastatic RCC patients likely to benefit from treatment with sorafenib.