Current status and future directions of molecular markers in renal cell carcinoma

Abstract

To describe the existing data regarding the prognostic and/or predictive value of molecular markers in metastatic renal cell carcinoma. Several molecular markers have been investigated in metastatic renal cell carcinoma for prognostic and/or predictive potential, many of which relate to pathogenic molecular alterations that are now therapeutic targets. Carbonic anhydrase IX is a von Hippel-Lindau (VHL)-mediated enzyme expressed in the majority of renal cell carcinoma tumors. High (>85%) expression of carbonic anhydrase IX in renal cell carcinoma tumors is a favorable prognostic marker and may predict response to interleukin-2 therapy. B7-H1 is a glycoprotein with inhibitory effects on T cells. B7-H1 expression in renal cell carcinoma tumor cells and/or lymphocytes may confer a worse survival in renal cell carcinoma patients, perhaps through impairment of inherent host of antitumor immunity. VHL pathway elements, including VHL gene status and expression of vascular endothelial growth factor protein and receptor, represent a promising area of investigation to predict responses to vascular endothelial growth factor-targeted agents. Prognostication schemas are beginning to incorporate molecular markers with clinical variables to refine the prediction of patient outcome. Several molecular markers appear promising to refine prognosis and prediction in metastatic renal cell carcinoma. Further prospective evaluation is needed.