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

Abstract

Tumour-infiltrating mast cells (TIMs) have been reported to play functional roles in the tumour 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 tumour-infiltrating lymphocytes (TILs) in patients with mRCC treated with sunitinib or sorafenib. Baseline clinical characteristics and follow-up data were collected from 231 patients with mRCC; 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=.008, and PFS, P=.016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS (HR=0.624, 95% CI: 0.420-0.927, P=.020) and PFS (HR=0.658, 95% CI: 0.466-0.930, P=.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=.002 and P=.004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8+ and CD4+ TILs (P=.008 and P=.001, respectively). Thus, better OS in patients with mRCC exhibiting a high mast cell density population may be attributed to the co-existence of CD8+ and CD4+ TILs, which have anti-tumour effects on activation status.