Introduction: Bone metastasis is a frequent event in patients with breast cancer. OPG (osteoprotegerin) protects bone from excessive resorption by binding to RANK-L (receptor activator of nuclear factor-kB-ligand) and by preventing it from binding to RANK. These molecules are closely involved in the process of metastasization to bone. CXCL12/SDF-1α, the ligand of CXCR4, is overexpressed in bone, and the local chemokine milieu is now emerging as a key determinant in organ selectivity by tumor cells. We carried out a retrospective analysis to evaluate the potential role of these biological markers in predicting bone metastasization in breast cancer patients.

Materials and methods: OPG and CXCR4 expression was determined by avidin-biotin immunohistochemistry using a polyclonal (H-249, Santa Cruz) and monoclonal (Ab58176, Abcam) antibody, respectively. Immunohistochemical staining was carried out on sections from paraffin-embedded blocks of 40 primary breast cancers. Ten patients (median age of 64 years, range 48-78) were disease-free (DF) at a median of 9.8 (range 6.9-11.5) years, while 30 (median age 67 years, range 42-87) had relapsed. In the latter group, 10 (median age 66 years, range 42-87) had visceral metastases (VM) and 20 (median age 69 years, range 42-87) had bone metastases (BM).

Results: Considering only strong cytoplasmic expression as positive, 22.5% of tumors were positive for OPG and 25% for CXCR4. In particular, OPG was expressed in 20% of tumors in DF patients and in 25% in BM patients. Conversely, CXCR4 was expressed in 10% of tumors in DF patients and in 45% in BM patients. OPG was expressed in only 20% of tumors in VM patients. There was no correlation between OPG and CXCR4 expression, and positivity to at least one of the two markers was observed in 30% of tumors in DF patients, 20% in VM patients and 55% in BM patients. In this last subgroup, there were no statistically significant associations between marker expression and tumor characteristics. Furthermore, no relation was observed between marker expression and disease-free or overall survival in BM patients.

Conclusions: Our preliminary results suggest that cytoplasmic CXCR4 expression in primary breast cancers could play a role in predicting bone metastases. Enrolment of breast cancer patients in a larger study is ongoing to confirm these data and to evaluate the predictive role of RANK and RANK-L in bone metastasization.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2241.