Expression of potential molecular markers in renal cell carcinoma: impact on clinicopathological outcomes in patients undergoing radical nephrectomy.

Abstract

To evaluate the expression levels of several potential molecular markers in renal cell carcinoma (RCC), to clarify the significance of these markers as prognostic predictors in patients undergoing radical nephrectomy (RN). The study included 153 patients with clinically organ-confined RCC undergoing RN. Expression levels of 12 proteins, including Aurora-A, Bcl-2, Bcl-xL, clusterin, heat-shock protein 27 (HSP27), HSP70, HSP90, Ki-67, matrix metalloproteinase (MMP)-2 and -9, p53 and vascular endothelial growth factor, in RN specimens obtained from these 153 patients were measured by immunohistochemical staining. Of the 12 markers, clusterin, HSP27, Ki-67, MMP-2 and -9 expression were significantly associated with several conventional prognostic factors. Univariate analysis also identified these five markers as significant predictors of disease recurrence, while mode of presentation, pathological stage, grade and microvascular invasion were also significant. Of these significant factors, Ki-67 expression, pathological stage and microvascular invasion appeared to be independently related to disease recurrence. Furthermore, there were significant differences in recurrence-free survival according to positive numbers of these three independent factors, i.e. disease recurred in four of 56 patients who were negative for risk factors (7%), 17 of 71 positive for one risk factor (24%), and 20 of 26 positive for two or three risk factors (77%). Combined evaluation of Ki-67 expression, pathological stage and microvascular invasion would be particularly useful for further refinement of the system for predicting the outcome after RN for patients with RCC.