Impact of RANK signalling on survival and chemotherapy response in osteosarcoma

Pathology. 2014 Aug;46(5):411-5. doi: 10.1097/PAT.0000000000000116.


The receptor activator of NF-κB (RANK) signalling pathway represents a promising target for the therapy of bone-related tumours. In the present study we evaluated the impact of the expression of RANK and its ligand (RANKL) on survival and response to chemotherapy in osteosarcoma patients.Expression of RANK and RANKL was examined in 91 human osteosarcomas by immunohistochemistry using formalin fixed, paraffin embedded (FFPE) tumour samples. Results of the stainings were correlated with clinicopathological parameters and patient survival.Sixty-three osteosarcomas (69.2%) expressed RANK, whereas only eight cases (8.8%) showed expression of RANKL. Expression of RANK was significantly associated with shorter disease-free survival by Kaplan-Meier analysis (p=0.031). We further observed worse response to chemotherapy in RANK expressing tumours, which was statistically not significant (p=0.099). RANKL expression was significantly more frequent in osteosarcoma of the lower extremity than in any other location. Analysis of RANKL expression did not reveal any statistically significant correlation with disease-free or osteosarcoma-specific survival.In our study, we identified RANK expression as a negative prognostic factor regarding disease-free survival in osteosarcoma. Moreover, RANK might modulate response of human osteosarcoma to chemotherapy. Therefore, RANK signalling cascade is likely to provide a novel alternative to targeted therapy of osteosarcoma and deserves further investigation.

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Child
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Osteosarcoma / drug therapy
  • Osteosarcoma / metabolism*
  • Osteosarcoma / mortality
  • Prognosis
  • Proportional Hazards Models
  • RANK Ligand / metabolism*
  • Receptor Activator of Nuclear Factor-kappa B / metabolism*
  • Signal Transduction / physiology
  • Young Adult


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • TNFRSF11A protein, human