To compare the histologic characteristics of residual renal cell carcinoma (RCC) following an interferon-alpha (IFN-alpha)-based therapy with clinical parameters, we examined 12 metastatic and 6 primary kidney tumors resected from 18 patients with advanced RCC. The histologic parameters including tumor necrosis, nuclear grade, inflammatory response and hemosiderin deposition were assessed. The immunophenotypes of tumorinfiltrating lymphocytes (TILs) were also characterized. The tumors of the 12 patients who had partial clinical response (responders) showed more tumor necrosis than the tumors of the 6 non-responders (patients with minor response or stable disease) (p = 0.0061). A tendency of longer overall survival was observed in the group with tumor necrosis compared to the group without necrosis. Predominance of T-cell TIL was demonstrated in all 9 responders compared to 3 non-responders (p = 0.053). Our findings suggest that tumor necrosis and a high percentage of T-cell TILs in residual RCC may be associated with favorable clinical response following IFN-alpha-based therapy.

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