title: Expression of receptor activator of nuclear factor kappa-B as a poor prognostic marker in breast cancer.
abstract: OBJECTIVE
  Receptor activator of nuclear factor kappa-B and its ligand (RANK/RANKL) and Osteoprotegerin (OPG) are key molecules for regulating osteoclastic activity in bone. However, little is known about the role of RANK-related molecules in breast cancer prognosis. We aimed to evaluate RANK, RANKL, and OPG expression and the associated clinical impact in breast cancer.
  
  
  METHODS
  Tissue microarray (TMA) from 185 patients with primary breast cancer was established. Immunohistochemistry for RANK, RANKL, and OPG was performed. Clinicopathologic features and survival outcomes associated with expression of RANK, RANKL, and OPG were analyzed.
  
  
  RESULTS
  RANK, RANKL, and OPG were expressed in 74.1%, 78.4%, and 45.9% of patients, respectively. RANKL expression was associated with lower Ki-67 level. OPG expression was related to small tumor size, node negativity, and low Ki-67. There was no significant difference in clinicopathologic features between tumors with RANK and those without RANK. RANK expression was significantly associated with poor disease-free survival in univariate analysis (P = 0.04) and multivariate analysis (P = 0.02). RANKL expression was associated with improved skeletal disease-free survival in multivariate analysis (P = 0.03).
  
  
  CONCLUSIONS
  The RANK/RANKL pathway regulated by OPG may have a role in predicting progression and prognosis of breast cancer.
authors.affiliation: Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Hyung Seok
authors.initials: HS
authors.lastname: Park
authors.forename: Ahwon
authors.initials: A
authors.lastname: Lee
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Chae
authors.forename: Ja-Seong
authors.initials: JS
authors.lastname: Bae
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Song
authors.forename: Sang Seol
authors.initials: SS
authors.lastname: Jung
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D053244:Osteoprotegerin / Q000378:metabolism*; D011379:Prognosis; D011446:Prospective Studies; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human
keywords: RANK ligand; breast neoplasms; osteoprotegerin; prognosis; receptor activator of nuclear factor-kappa B; survival