Role of RANK, RANKL, OPG, and CXCR4 tissue markers in predicting bone metastases in breast cancer patients

Toni Ibrahim, Emanuele Sacanna, Michele Gaudio, Laura Mercatali, Emanuela Scarpi, Wainer Zoli, Patrizia Serra, Rossana Ricci, Luigi Serra, Yibin Kang, Dino Amadori

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

Background: The RANK/RANKL/OPG system is active in primary cancers such as breast, prostate, and also in their bone metastases. CXCR4 chemokine receptor is highly expressed in human breast cancer cells and is believed to facilitate the homing of tumor cells to organs such as bone that express high levels of its ligand SDF1. Our study aimed to investigate whether the analysis of these markers with an inexpensive and simple test can help to predict bone metastases in breast cancer patients. Patients and Methods: Marker expression was evaluated by immunohistochemical staining in paraffin-embedded tissue sections of primary breast cancers from 40 individuals: 20 patients with bone metastases (BM), 10 with visceral metastases (VM; considered together as the relapsed group), and 10 with no evidence of disease (NED). Results: RANKL was not detected in tumor cells. OPG- and RANK-positive tumors are found with similar frequency in NED (20%) and in relapsed patients (23% and 17%, respectively). However, in the latter subgroup, only RANK positivity was always associated with bone relapse. The frequency of CXCR4-positive tumors was three-fold higher in relapsed (30%) than in NED (10%) patients and positivity was always linked to bone metastases. Considering NED and VM patients together versus BM patients, we observed that CXCR4 expression, alone (P =.008) or in combination with RANK (P <.001), identified patients destined to relapse to bone. Conclusion: Our results provide the first clinical evidence to support a pivotal role of combined CXCR4 and RANK expression in predicting bone relapse.

Original languageEnglish (US)
Pages (from-to)369-375
Number of pages7
JournalClinical Breast Cancer
Volume11
Issue number6
DOIs
StatePublished - Jan 1 2011

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Keywords

  • Bone metastases
  • Breast cancer
  • CXCR4
  • OPG
  • RANK/RANKL

Fingerprint Dive into the research topics of 'Role of RANK, RANKL, OPG, and CXCR4 tissue markers in predicting bone metastases in breast cancer patients'. Together they form a unique fingerprint.

  • Cite this

    Ibrahim, T., Sacanna, E., Gaudio, M., Mercatali, L., Scarpi, E., Zoli, W., Serra, P., Ricci, R., Serra, L., Kang, Y., & Amadori, D. (2011). Role of RANK, RANKL, OPG, and CXCR4 tissue markers in predicting bone metastases in breast cancer patients. Clinical Breast Cancer, 11(6), 369-375. https://doi.org/10.1016/j.clbc.2011.05.001