Jornal de Biomarcadores Moleculares e Diagnóstico

Prognostic Role of RANK and RANKL Expression in Recurrent Giant Cell Tumor of Bone: A Retrospective Study

Abstract

Nannaphat Atsawaphidsawat, Piti Ungarreevittaya, and Chat Sumananont

Objective: Giant cell tumor of bone (GCTB) is a benign locally aggressive primary bone tumor with a tendency for recurrence which is one of the major problems in this disease. Recent data demonstrated the important role of the receptor activator of nuclear factor-κB (RANK)/RANK-ligand (RANKL) pathway in the pathogenesis. However, the roles of RANK and RANKL in predicting recurrence have never been proposed. Therefore, we aim to investigate the prognostic value of RANK and RANKL expression in predicting recurrence of GCTB which may change the treatment paradigm of the disease. Method: 53 cases of GCTB were enrolled in the study. Data on patient demographics and clinical characteristics were reviewed. Immunohistochemistry was used to detect the expression of RANK and RANKL. Recurrence-free survival (RFS) analysis was performed by Kaplan–Meier method and the difference between survival curves were sought using the log-rank test. Cox’s proportional hazards model and binary logistic regression analyses were used to define the risk of recurrence. Result: Of 53 cases, there were 8 patients (15.1%) had recurrent disease. The univariate analysis revealed that age (log rank 10.749, p=0.005), RANKL overexpression (log rank 5.187, p=0.023), RANK overexpression (log rank 4.055, p=0.044 for RANK) and co-overexpression of RANK/RANKL (log rank 7.541, p<0.006) were associated with recurrence of GCTB. Cox’s proportional hazards model emerged that the only significant prognostic parameter capable of defining the risk for recurrence was co-overexpression of RANK and RANKL (Hazard ratio 2.910; 95%CI 1.099-7.708; p= 0.032). Binary logistic regression multivariate analysis followed by ROC analysis confirmed that cooverexpression of RANK/RANKL represented a significant biological model to predict local recurrence (area under the curve=0.731±0.098; 95% CI 0.539–0.922, p=0.039). Conclusion: RANK and RANKL co-overexpression increases the risk of recurrence of GCTB and could be a prognostic marker for recurrent disease.