Expression of enamel proteins and LEF1 in adamantinomatous craniopharyngioma: evidence for its odontogenic epithelial differentiation.
OBJECTIVE
Adamantinomatous craniopharyngioma (ACP) resembles histologically some odontogenic tumours, such as ameloblastoma and calcifying odontogenic cyst. However, there has been no evidence that ACP differentiates also functionally as odontogenic epithelium. The aim of this study was to gain evidence of odontogenic epithelial differentiation in ACP by means of immunohistochemistry. Among normal human tissues, enamel proteins are expressed exclusively in teeth, and lymphoid enhancer factor 1 (LEF1), in co-operation with beta-catenin, play an important role in tooth development. The expression of these proteins is therefore indicative of odontogenic epithelial differentiation.


RESULTS
The expression of enamel proteins and LEF1 was examined in 10 adamantinomatous and six papillary craniopharyngiomas. All the ACPs showed a variable degree of enamel protein expression, including amelogenin, enamelin and enamelysin, mainly in ghost cells. LEF1 was also heterogeneously expressed in ACPs; remarkably, its expression pattern was identical to that of nuclear beta-catenin accumulation. In contrast, none of the papillary craniopharyngiomas expressed enamel proteins or LEF1.


CONCLUSIONS
These results suggest that ACP consistently shows odontogenic epithelial differentiation. Since ACPs harbour beta-catenin mutation, the inappropriate activation of beta-catenin/LEF1 complex-dependent transcription may play a critical role in ACP tumorigenesis.
Sekine
S
S
Pathology Division, National Cancer Center Research Institute, Tokyo, Japan.
Takata
T
T
Shibata
T
T
Mori
M
M
Morishita
Y
Y
Noguchi
M
M
Uchida
T
T
Kanai
Y
Y
Hirohashi
S
S
D000328:Adult; D000368:Aged; D000564:Ameloblastoma / Q000378:metabolism / Q000473:pathology*; D053523:Amelogenin; D002291:Carcinoma, Papillary / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D003397:Craniopharyngioma / Q000378:metabolism / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D003746:Dental Enamel Proteins / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D051821:Lymphoid Enhancer-Binding Factor 1; D008297:Male; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases / Q000032:analysis; D008875:Middle Aged; D015534:Trans-Activators / Q000032:analysis; D014157:Transcription Factors / Q000096:biosynthesis*; D051176:beta Catenin
D053523:Amelogenin; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D003746:Dental Enamel Proteins; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D015534:Trans-Activators; D014157:Transcription Factors; D051176:beta Catenin; C038456:tuftelin; C507111:MMP20 protein, human; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases