title: Notch4 overexpression in ameloblastoma correlates with the solid/multicystic phenotype.
abstract: OBJECTIVE
  Notch signaling has been implicated in cell fate decisions during odontogenesis and tumorigenesis of some odontogenic neoplasms; however, its role in solid/multicystic (SA), unicystic (UA), and recurrent (RA) ameloblastoma remains unclear. The aim of this study was to determine Notch receptor and ligand expressions in these subtypes and to speculate on their significance.
  
  
  METHODS
  Notch receptors (Notch1, 2, 3, 4) and ligands (Jagged1, 2, and Delta1) were examined immunohistochemically in SA (n = 23), UA (n = 22), and RA (n = 19).
  
  
  RESULTS
  Notch4 overexpression in SA (n = 19/23; 82.6%) compared with UA (n = 1/22; 4.5%) or RA (n = 10/19; 52.6%) (P < .05) suggests positive correlation between Notch4 signaling and ameloblastomas with a solid/multicystic phenotype. Ligand (Jagged1 and Delta1) underexpression compared with their receptors (Notch1, 3, 4) (P < .05) and nonreactivity for Notch2 and Jagged2 in all 3 subsets suggests that ameloblastoma epithelium belongs to an earlier stage of differentiation (equivalent to inner enamel epithelium of developing tooth germ) before lineage commitment.
  
  
  CONCLUSIONS
  Present findings suggest that Notch signaling molecules may play differing roles in the acquisition of different ameloblastoma phenotypes.
authors.affiliation: Department of Oral Pathology, Oral Medicine, and Periodontology, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. siarch@um.edu.my
authors.forename: Chong Huat
authors.initials: CH
authors.lastname: Siar
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nagatsuka
authors.forename: Kee Seng
authors.initials: KS
authors.lastname: Chuah
authors.forename: Rosario Santos
authors.initials: RS
authors.lastname: Rivera
authors.forename: Keisuke
authors.initials: K
authors.lastname: Nakano
authors.forename: Kok Han
authors.initials: KH
authors.lastname: Ng
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kawakami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000564:Ameloblastoma / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004848:Epithelium / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008024:Ligands; D008297:Male; D008339:Mandibular Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008441:Maxillary Neoplasms / Q000145:classification / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000096:biosynthesis* / Q000235:genetics; D018709:Statistics, Nonparametric; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch