RANKL expression is related to treatment outcome of patients with localized, high-grade osteosarcoma

Background The receptor activator of nuclear factor κB ligand (RANKL/TNFSF11) is expressed in metastatic bone cancer cells and has been suggested to play a key role in cell migration and metastatic behavior. We determined whether RANKL expression is correlated to clinical behavior of localized, high‐grade osteosarcoma. Patients and methods This retrospective, immunohistochemical study was performed using materials obtained from 40 patients treated at Korea Cancer Center Hospital between 1995 and 2007. Prechemotherapy biopsy samples were stained for RANKL and correlations between RANKL expression and clinical characteristics and outcomes were evaluated. Staining was interpreted in a semiquantitative manner using an intensity based scoring system. Results Thirty cases (75.0%) stained positively for RANKL; 15 (50.0%) had a high RANKL score (≥ 4) and the other 15 a low RANKL score (≤3). RANKL expression and RANKL scores were not related to age, sex, tumor location, tumor volume, or pathologic subtype. However, RANKL expression was related to a poor response to preoperative chemotherapy (P = 0.03) and a high RANKL score was associated with inferior survival. The 5‐year event‐free survival of patients with RANKL score ≥4 was 17.8 ± 10.5%, which was far worse than those with RANKL scores 1–3 or 0 (50.0 ± 15.8%, 56.0 ± 13.7%, respectively, P = 0.02). Conclusions The RANKL–RANK–OPG axis might be a promising target for the treatment of osteosarcoma, but further studies are needed to verify our data in a larger cohort. Pediatr Blood Cancer 2011;56:738–743. © 2010 Wiley‐Liss, Inc.