Twofold Expression of Receptor Tyrosine Kinase 2 (ROR2) in Giant Cell Tumors of Bone: Outcome of a Case‒Control Study.

Suppression or overexpression of transmembrane proteins of the Wnt family and receptor tyrosine kinases (ROR1 and ROR2) is implicated in the causation of cancer. The objective of this study was to determine the expression of ROR2 in patients with giant cell tumor of bone (GCT) by quantitative PCR (qPCR). In this case‒control study, samples of tumor tissue (patients) and bone from the tumor-free margin (controls) were subjected to qPCR in patients who underwent definitive treatment. The GCTs were classified per radiologic classification and histologic grading. Eleven cases and controls, consisting of six men and five women with a mean age of 33.18 ± 12.35 (20-50) years, were included over the study period of 2 years. The median duration since diagnosis was 12 (IQR 9) months. There was a 2.51-fold change (upregulation of ROR2 expression) in cases compared with controls, which was significant (0.00). There was an increase in the expression of ROR2 with tumor grade. However, these differences were not significant (Campanacci (P 0.05 cases and 0.84 controls), Jaffe (P 0.07 cases and 0.44 controls), or Enneking (0.07 cases and 0.44 controls)). Treatment with bisphosphonates (P = 0.17) or denosumab (P = 0.75) had no significant effect on ROR2 expression. Patients with GCT exhibit more than twofold upregulation of ROR2 expression, confirming its role in causing osteoclast-mediated bone destruction. Therefore, ROR2 may be a target for drug development in the treatment of GCT.