Sympathetic innervation of renal cell carcinomas and their environment, a pilot study

Sympathetic nerves are a common feature in tumors; in the tumor microenvironment and in mouse models, they have been implicated in tumor initiation and progression. Clinical studies report an association between increased nerve density and adverse tumor characteristics in various carcinomas. So far, no studies have been published in renal cell carcinoma (RCC). The aim of this study is to quantify sympathetic nerves in RCC and its environment.

We quantified sympathetic nerve density in 10 T1a RCCs, 5 metastatic lesions, and 8 normal kidney tissues. Histopathological analysis and immunohistochemistry with antibodies against tyrosine hydroxylase (TH) were performed.

In normal kidney, autonomic nerves were mainly sympathetic. Within the T1a tumors, the percentage of TH-positive pixels of sympathetic nerves was low (0.03 +/- 0.05), and very low in metastases (0.001 +/- 0.003). A remarkable high-density pattern of sympathetic fibers was found in the vicinity of two T1a tumors. More distant (> 2mm), the percentage of TH-positive pixels was similar to that of controls (0.11 +/- 0.10).

We observed a low density of sympathetic nerves within T1a renal tumors and metastatic lesions compared with normal kidney tissue. An increased density of sympathetic nerves was seen in the direct vicinity of two tumors. These preliminary results in this small pilot cohort suggest that in RCC, increased sympathetic nerve density may be encountered in the tumor environment but not the tumor itself.