P3-01-12: Prognostic Impact of RANK, RANKL and OPG Gene Expression in ER Positive Primary Breast Cancer.

Abstract

Abstract Background The cell surface receptor RANK (receptor activator of NFκB), its ligand (RANKL) and the decoy receptor of RANKL osteoprotegerin (OPG) play an important functional role in bone physiology and in bone metastasis by regulating osteoclasts. Just recently it was shown that tumor-infiltrating lymphocytes can stimulate breast cancer metastases through RANK-RANKL signalling. Material and methods: We analyzed gene expression of RANK, RANKL and OPG in a combined Affymetrix dataset of 307 ER positive breast cancers from our institutions which were either untreated of treated with chemotherapy. Kaplan Meier analysis of disease free survival and Cox regression analysis was applied to examine the prognostic value of the different markers. Results: We observed no significant difference in survival when samples were analyzed according to either RANK or RANKL mRNA expression. In contrast when samples were stratified in quartiles of OPG expression a positive linear relationship of survival with the expression of OPG was observed. Moreover since OPG demonstrated a bimodal type of expression a cutoff value can be derived from the expression data. Using this cutoff value a hazard ration of 2.14 (95% CI 1.27−3.61; P=0.004 for low OPG expression was detected. OPG expression correlated with lower proportion of grade 3 tumors (15.7% vs 27%; P=0.022) and a higher proportion of PgR positive samples (86.2% vs 71.4%; P=0.002). No significant differences were observed for lymph node status, age, tumor size and HER2 status. In multivariate analysis only lymph node status remained significant while OPG, Ki67, age, grade, and PgR only displayed a trend towards significance. Conclusion: Expression of osteoprotegerin seems to correlate with good prognosis in ER postive breast cancer. These data are in line with in vitro studies demonstration that OPG inhibits RANKL induced migration of tumor cells. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-01-12.