Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in Nonmetastatic Clear-Cell Renal Cell Carcinoma.

PURPOSE: The role played by the innate immune system in determining the clinical outcome of clear-cell renal cell carcinoma (ccRCC) was still blurred. This study was designed to investigate the prognostic significance of tumor infiltrating mast cells (TIMs) in ccRCC.

METHODS: The study retrospectively enrolled a training set (474 patients) and a validation set (188 patients) with nonmetastasis (pT1-4N0M0) ccRCC from two institutional medical centers of China. TIMs was evaluated by immunohistochemical staining of tryptase and its association with clinicopathologic features and prognosis were evaluated.

RESULTS: In ccRCC tissues, TIMs ranged from 0 to 103 cells/mm2 and 0 to 113 cells/mm2 in the training set and validation set, respectively. TIMs was negatively correlated with tumor size (P < 0.001 and P < 0.001, respectively), pathological T stage (P = 0.005 and P = 0.007, respectively) and Fuhrman grade (P < 0.001 and P < 0.001, respectively). Patients with abundant TIMs infiltration showed significantly longer cancer-specific survival in the training cohort and the validation cohort (P < 0.001 and P < 0.001). Patients with abundant mast cell infiltration showed significantly longer overall survival in the TCGA cohort (P < 0.001). Moreover, multivariate analysis identified TIMs as an independent prognostic factor for cancer-specific survival (CSS) and relapse-free survival (RFS). Also, TIMs was significantly correlated with CSS and RFS of the mediate and high-risk patients in the training cohort and the validation cohort.

CONCLUSIONS: TIMs density is a powerful independent prognostic factor for CSS and RFS in patients with nonmetastasis (pT1-4N0M0) ccRCC.