Mast cell density in metastatic renal cell carcinoma: Association with prognosis and tumor infiltrating lymphocytes.

Tumor infiltrating mast cells (TIMs) have been reported to play functional roles in the tumor microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumor infiltrating lymphocytes (TILs) in mRCC patients treated with sunitinib or sorafenib. Baseline clinical characteristics and follow-up data were collected from 231 mRCC patients; TIMs (mast cells density positive to tryptase), along with CD8+ and CD4+ TILs, were evaluated by immunohistochemistry using a tissue microarray. The log-rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression-free survival (OS, p=0.008, and PFS, p=0.016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS and (HR=0.624, 95% CI: 0.420-0.927, p=0.020) and PFS (HR=0.658, 95% CI: 0.466-0.930, p=0.019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one- and two-year OS (p=0.002 and p=0.004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8+ and CD4+ TILs (p=0.008 andp=0.001, respectively). Thus, better OS in mRCC patients exhibiting an high mast cell density population may be attributed to the co-existence of CD8+ and CD4+ TILs, which have anti-tumor effects on activation status.