Altered expression of cell-cell adhesion molecules β-catenin/E-cadherin and related Wnt-signaling pathway in sporadic and syndromal keratocystic odontogenic tumors.
Differential diagnosis of the keratocystic odontogenic tumor (KCOT) still represents a challenging problem especially if compared with the dentigerous cyst, which is similar in clinical and radiological course. Histological assessment of this entity may therefore draw crucial attention since various radical procedures are recommended for such lesions in contrast to dentigerous cysts. Since recent reports could prove the involvement of wingless(Wnt)-signaling pathway and β-catenin in the pathogenesis of many odontogenic and neoplastic lesions indicating impairment of cell-cell adhesion, we investigated the expression of two Wnt-signaling pathways, Wnt-1 and Wnt-10A as well as β-catenin and E-cadherin along with other related proteins in both lesions. We found a significant down-regulation in the expression of cell adhesion proteins β-catenin and E-cadherin along with alteration of Wnt-1 and Wnt-10A expression in the epithelium of KCOT. We assessed a specific focal distribution pattern of p63 in the suprabasal cell layer and a significant up-regulation of cyclin D1. Furthermore, laminin α-2 was a characteristic marker labelling only the basement membrane of dentigerous cysts. These results provide a new hypothesis explaining a molecular mechanism to understand initiating and development of KCOTs and an alternative therapeutic approach, especially for syndromal patients, where these multilocal lesions may involve and destroy wide orofacial bony structures.
Hakim
Samer George
SG
Department of Oral and Maxillofacial Surgery, University of Lübeck, Lübeck, Germany. samer.hakim@mkg-chir.mu-luebeck.de
Kosmehl
Hartwig
H
Sieg
Peter
P
Trenkle
Thomas
T
Jacobsen
Hans-Christian
HC
Attila Benedek
Geza
G
Ribbat
Julika
J
Driemel
Oliver
O
D001478:Basal Cell Nevus Syndrome / Q000473:pathology; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D003803:Dentigerous Cyst / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D003937:Diagnosis, Differential; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D007797:Laminin / Q000096:biosynthesis; D009808:Odontogenic Tumors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D019063:Tenascin / Q000096:biosynthesis; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
D015820:Cadherins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007797:Laminin; D019063:Tenascin; C484142:WNT10A protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D051176:beta Catenin; C102645:laminin alpha 2