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Receptor activator of nuclear factor κB (RANK), a member of the tumour necrosis factor family, is activated by its ligand and regulates the differentiation of osteoclasts and dendritic cells. Local growth of osteosarcoma involves destruction of the host bone by osteoclasts and proteolytic mechanisms. Although the prognosis of patients with osteosarcoma has been improved by advances in chemotherapy over the last four decades, the issues of non-responders, and the lack of effective prognostic markers have remained. The present study aimed to investigate the prognostic and predictive value of RANK expression in human osteosarcoma. The expression of RANK was immunohistochemically evaluated in biopsies of 43 patients (mean age 25.4 years) with high-grade osteosarcoma, and was found to be correlated with histological response to chemotherapy, disease-free status and overall survival. RANK expression was detected in eight of the 43 osteosarcoma specimens (18%), whereas the remaining specimens were negative for RANK. A statistically significant correlation was detected between RANK expression and the overall survival of patients. A total of 7/8 patients with RANK-expressing tumours succumbed to the disease (88% mortality rate amongst patients with RANK-positive tumours vs. 37% with RANK-negative tumours; P&lt;0.05). No significant difference was found when comparing RANK expression status with response to chemotherapy; 50% of RANK-positive patients exhibited a poor response to chemotherapy, compared with 66% in the RANK negative group. In addition, the appearance of metastases was not correlated with RANK expression status (38% metastases in RANK-positive tumours vs. 34% in RANK-negative tumours). In conclusion, the results of the present study suggested that RANK expression is likely to be of prognostic, but not of predictive, value.

Receptor activator of nuclear factor κB expression is a prognostic factor in human osteosarcoma