title: Upregulation of osteoprotegerin expression correlates with bone invasion and predicts poor clinical outcome in oral cancer.
abstract: OBJECTIVE
  We aimed to determine the prognostic significance of receptor activator of nuclear factor kappa-B ligand (RANKL), RANK and osteoprotegerin (OPG) in patients with oral squamous cell carcinoma (OSCC).
  
  
  METHODS
  The protein expression of RANKL, RANK and OPG was assessed by immunohistochemistry on pretreatment biopsies of 93 patients with locally advanced OSCC who received preoperative chemoradiotherapy (CRT). The primary endpoint was cancer-specific survival. Secondary endpoints were correlation of biomarkers with bone invasion and pathological tumor response. Kaplan-Meier curves and Cox regression models were used for survival analyses.
  
  
  RESULTS
  A significantly higher OPG expression was demonstrated in patients with malignant bone invasion and non-responders to CRT as compared to patients without bone invasion and responders (p=0.032 and p=0.033, respectively). Multivariate analysis revealed that higher OPG expression was independently associated with shorter cancer-specific survival (p=0.04). The expression status of RANKL and RANK was not significantly related to clinicopathological characteristics and had no impact on survival of OSCC patients.
  
  
  CONCLUSIONS
  Upregulation of OPG expression is associated with bone invasion, poor pathological tumor regression to neoadjuvant CRT, and worse long-term cancer-specific survival in patients with locally advanced OSCC. Our results indicate that OPG may be a novel prognostic biomarker in oral cancer.
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Russmueller
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Moser
authors.affiliation: Department of Clinical Pathology, Medical University of Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Würger
authors.affiliation: Department of Clinical Pathology, Medical University of Vienna, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Wrba
authors.affiliation: Department of Maxillofacial and Oral Surgery, University of Athens, Greece. Electronic address: christos.perisanidis@meduniwien.ac.at.
authors.forename: P
authors.initials: P
authors.lastname: Christopoulos
authors.affiliation: Department of Maxillofacial and Oral Surgery, University of Athens, Greece.
authors.forename: G
authors.initials: G
authors.lastname: Kostakis
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: Seemann
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: V
authors.initials: V
authors.lastname: Stadler
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Wimmer
authors.affiliation: Department of Medicine I, Medical University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Kornek
authors.affiliation: Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Psyrri
authors.affiliation: Department of Medicine I, Institute of Cancer Research, Medical University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Filipits
authors.affiliation: Department of Cranio-, Maxillofacial and Oral Surgery, Medical University of Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Perisanidis
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D053244:Osteoprotegerin / Q000378:metabolism*; D011379:Prognosis; D053245:RANK Ligand / Q000378:metabolism*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D053244:Osteoprotegerin; D053245:RANK Ligand
keywords: Neoadjuvant therapy; Oral cancer; Osteoprotegerin; Prognosis; RANK ligand; Receptor activator of nuclear factor-kappa B