Prediction of response to combined immunotherapy with interferon-α and low-dose interleukin-2 in metastatic renal cell carcinoma: Expression patterns of potential molecular markers in radical nephrectomy specimens

Objectives:   To evaluate the expression levels of multiple molecular markers in radical nephrectomy specimens from patients with metastatic renal cell carcinoma (RCC) who received combined immunotherapy with interferon-α (IFN-α) and low-dose interleukin-2 (IL-2) and to identify factors predicting susceptibility to this therapy.
Methods:   This study included 40 patients with metastatic clear cell RCC undergoing combined immunotherapy with IFN-α and low-dose IL-2 following radical nephrectomy. Expression levels of 10 markers, including Aurora-A, Bcl-2, clusterin, heat shock protein 27, heat shock protein 90, Ki-67, matrix metalloproteinase-2, matrix metalloproteinase-9, p53 and vascular endothelial growth factor, in RCC specimens were measured using immunohistochemical staining.
Results:   In this series, one, 10, 15 and 16 patients were diagnosed as showing complete response, partial response, stable disease and progressive disease, respectively. Expression levels of Bcl-2 and Ki-67 had significant impacts on the response to this therapy. Furthermore, cancer-specific survival was significantly associated with the expression levels of Ki-67 and Bcl-2 in addition to performance status, presence of metastases at diagnosis, metastatic organ and C-reactive protein on univariate analysis. Only the presence of metastases at diagnosis and Ki-67 expression level appeared to be independent predictors of cancer-specific survival on multivariate analysis.
Conclusions:   It would be useful to consider the expression levels of potential molecular markers, particularly Ki-67, in addition to clinical parameters, such as the presence of metastases at diagnosis, to select metastatic RCC patients likely to benefit from combined immunotherapy.