Differential expression of TIM-3 between primary and metastatic sites in renal cell carcinoma

Due to the significant heterogeneity of renal cell carcinoma (RCC), immune checkpoints may express differently between primary and metastatic tumor. We aimed to evaluate the differential expression of TIM-3 between the primary and metastatic sites of RCC.

Cases of RCC with metastases resected or biopsied at West China Hospital between January 2009 and November 2016 were included. Clinicopathological parameters were retrospectively extracted. SPPS 22.0, GraphPad Prism 6 and R statistical software were applied for data analysis.

A total of 163 cases were included. Immunohistochemical results showed that the overall detection rate of TIM-3 was 56.4% (92/163). The detection rate of TIM-3 in the primary (53.0%, 44/83) was numerically higher than that of the metastasis (42.6%,79/174). Although the concordance rate of TIM-3 between the primary and metastasis was as high as 66.3% (55/83) in the paired cohort, a significant statistically difference of TIM-3 expression between the primary and metastasis was observed (χ2 = 4.664, p = 0.002), with a poor consistency (Kappa = 0.331, p = 0.002). Subsequent survival analysis suggested that TIM-3 expression either in the primary or metastatic tumor was associated with longer progression-free survival (PFS) (HR: 0.67, 95% CI 0.45–0.99, P = 0.02) and overall survival (OS) (HR: 0.52, 95% CI 0.33–0.82, P < 0.001). The expressions of TIM-3 in the primary, metastatic tumors and patients treated with targeted agents all played as favorable factors for PFS and OS. Further multivariate analysis showed that, in the whole cohort, TIM-3 expression in metastatic tumor increased the predicted accuracy (PA) of the whole model of PFS from 74.7 to 75.6% (P = 0.02). For OS, the PA of whole model was increased from 78.1 to 81.1% by adding TIM-3 expression in the metastasis (P = 0.005). The same trends were also observed in paired patients and patients treated with targeted agents. In conclusion, the expression difference between the primary and metastatic tumor of TIM-3 was significant. Biopsy or resection of the metastases may provide a more accurate biological information for clinician’s decision-making and the patient’s prognosis. What’s more, the role of TIM-3 in the RCC still remains controversy, further study are needed to verify the conclusion.