Perineural invasion: a potential reason of hepatocellular carcinoma bone metastasis

The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. Perineural invasion (PNI) is the only interaction between cancer cells and nerves studied to date. It is a symbiotic relationship between cancer cells and nerves that result in growth advantage for both. The potential association between HCC bone metastases and PNI is unknown. In this study, we investigate the nerve density in HCC and paired bone metastases to reveal the potential association of HCC bone metastases and PNI. The nerve density was evaluated by immunohistochemistry in formalin-fixed paraffin embedded (FFPE) hepatocellular carcinoma (HCC) and paired bone metastases tissues from 13 HCC patients with synchronous or metachronous bone metastases that underwent surgical resection. FFPE specimens of HCC bone metastases tissues express higher perineural density than HCC tissues, pointing to a potential role of the PNI in bone metastases from HCC. This is the first description of the potential association of PNI and HCC bone metastases.