title: Differential expression of canonical and non-canonical Wnt ligands in ameloblastoma.
abstract: BACKGROUND
  Canonical and non-canonical Wnt signaling pathways modulate diverse cellular processes during embryogenesis and post-natally. Their deregulations have been implicated in cancer development and progression. Wnt signaling is essential for odontogenesis. The ameloblastoma is an odontogenic epithelial neoplasm of enamel organ origin. Altered expressions of Wnts-1, -2, -5a, and -10a are detected in this tumor. The activity of other Wnt members remains unclarified.
  
  
  METHODS
  Canonical (Wnts-1, -2, -3, -8a, -8b, -10a, and -10b), non-canonical (Wnts-4, -5a, -5b, -6, 7a, -7b, and -11), and indeterminate groups (Wnts-2b and -9b) were examined immunohistochemically in 72 cases of ameloblastoma (19 unicystic [UA], 35 solid/multicystic [SMA], eight desmoplastic [DA], and 10 recurrent [RA]).
  
  
  RESULTS
  Canonical Wnt proteins (except Wnt-10b) were heterogeneously expressed in ameloblastoma. Their distribution patterns were distinctive with some overlap. Protein localization was mainly membranous and/or cytoplasmic. Overexpression of Wnt-1 in most subsets (UA = 19/19; SMA = 35/35; DA = 5/8; RA = 7/10) (P < 0.05), Wnt-3 in granular cell variant (n = 3/3), and Wnt-8b in DA (n = 8/8) was key observations. Wnts-8a and -10a demonstrated enhanced expression in tumoral buddings and acanthomatous areas. Non-canonical and indeterminate Wnts were absent except for limited Wnt-7b immunoreactivity in UA (n = 1/19) and SMA (n = 1/35). Stromal components expressed variable Wnt positivity.
  
  
  CONCLUSIONS
  Differential expression of Wnt ligands in different ameloblastoma subtypes suggests that the canonical and non-canonical Wnt pathways are selectively activated or repressed depending on the tumor cell differentiation status. Canonical Wnt pathway is most likely the main transduction pathway while Wnt-1 might be the key signaling molecule involved in ameloblastoma tumorigenesis.
authors.affiliation: Department of Oral Pathology, Oral Medicine & 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: Phuu Pwint
authors.initials: PP
authors.lastname: Han
authors.forename: Rosario Rivera
authors.initials: RR
authors.lastname: Buery
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Tsujigiwa
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*; D002648:Child; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006023:Glycoproteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics*; D060449:Wnt Signaling Pathway / Q000235:genetics; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein / Q000235:genetics; D051154:Wnt2 Protein / Q000235:genetics; D060508:Wnt3 Protein / Q000235:genetics; D060528:Wnt4 Protein / Q000235:genetics; D055815:Young Adult
chemical_list: D006023:Glycoproteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; C484142:WNT10A protein, human; C491119:WNT10B protein, human; C495244:WNT2 protein, human; C115496:WNT2B protein, human; C555507:WNT3 protein, human; C555581:WNT4 protein, human; C085389:WNT5A protein, human; C435831:WNT5B protein, human; C490674:WNT6 protein, human; C092778:WNT7A protein, human; C490675:WNT7B protein, human; C490604:WNT8B protein, human; C449090:WNT9B protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051155:Wnt1 Protein; C540523:Wnt11 protein, human; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060528:Wnt4 Protein