title: RANK, RANKL, and OPG in recurrent solid/multicystic ameloblastoma: their distribution patterns and biologic significance.
abstract: OBJECTIVE
  To determine the distribution patterns of bone resorption regulators, receptor activator of nuclear factor κ-B (RANK), RANK ligand (RANKL), and osteoprotegerin (OPG) in recurrent ameloblastoma (RAs) and to clarify their impact on the biologic behavior of these neoplasms.
  
  
  METHODS
  Fifteen paraffin-embedded RA cases were subjected to immunohistochemistry for expression of RANK, RANKL, and OPG.
  
  
  RESULTS
  The RANK-RANKL-OPG triad was heterogeneously detected in RA samples. RANK, essential for osteoclast differentiation, was strongly expressed in tumoral epithelium. Conversely, RANKL, an osteoclast activator, was markedly underexpressed, and protein localization was predominantly stromal. OPG, an osteoclastogenesis inhibitory factor, was detected in neoplastic epithelium more than in stroma, suggesting functional inactivation of RANKL. Most RA (n = 12/15; 80%) exhibited a bimolecular spatial expression pattern, the most common being RANK-positive/OPG-positive (n = 8/15; 53.3%). All three proteins showed no significant correlation with the clinical/histopathologic parameters in RA patients (P > .05).
  
  
  CONCLUSIONS
  The RANK(+)/RANKL(low/-)/OPG(+) phenotype observed in RA suggests an altered local bone metabolism characterized by low bone resorptive activity in these recurrent tumors.
authors.affiliation: Professor of Oral Pathology and Oral Medicine, Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: Siarch@um.edu.my.
authors.forename: Chong Huat
authors.initials: CH
authors.lastname: Siar
authors.affiliation: Professor of Histopathology, Laboratory of Histopathology, Department of Life Science, Faculty of Science, Okayama University of Science, Okayama, Japan.
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
authors.affiliation: Senior Lecturer and Consultant Oral and Maxillofacial Surgeon, Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Ismadi
authors.initials: I
authors.lastname: Ishak
authors.affiliation: Master of Clinical Dentistry (Oral Medicine and Oral Pathology) Resident, Department of Oro-Maxillofacial Surgical and Medical Sciences, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Nurmawarnis Mat
authors.initials: NM
authors.lastname: Hussin
authors.affiliation: Professor of Oral Pathology and Medicine, Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.affiliation: Former Director and Senior Consultant Oral Pathologist, Unit of Stomatology, Institute for Medical Research, Jalan Pahang, Kuala Lumpur, Malaysia.
authors.forename: Kok Han
authors.initials: KH
authors.lastname: Ng
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000564:Ameloblastoma / Q000473:pathology* / Q000601:surgery; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008339:Mandibular Neoplasms / Q000473:pathology* / Q000601:surgery; D008875:Middle Aged; D053244:Osteoprotegerin / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human