Notch4 overexpression in ameloblastoma correlates with the solid/multicystic phenotype.
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.
Siar
Chong Huat
CH
Department of Oral Pathology, Oral Medicine, and Periodontology, Faculty of Dentistry, University of Malaya, Kuala Lumpur, Malaysia. siarch@um.edu.my
Nagatsuka
Hitoshi
H
Chuah
Kee Seng
KS
Rivera
Rosario Santos
RS
Nakano
Keisuke
K
Ng
Kok Han
KH
Kawakami
Toshiyuki
T
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
D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch