Beta-catenin gene alterations in a variety of so-called calcifying odontogenic cysts

Calcifying odontogenic cysts (COCs) evidence a variety of histopathological features, in addition to biological behaviors. Several systems have been proposed for the classification of COCs. However, the molecular changes underlying their development remain largely unknown. In an effort to elucidate the participation of beta-catenin gene mutation in COC development, we evaluated the genetic alterations and expression of beta-catenin in different COC subtypes with archival paraffin blocks. beta-catenin gene mutations were detected in all subtypes. Immunohistochemically, all cases of COCs evidenced cytoplasmic and nuclear beta-catenin expression. Beta-catenin gene mutations and beta-catenin overexpression have been identified as characteristics of COCs. Therefore, the constitutive activation of Tcf/Lef-dependent transcription appears to be intimately involved in their development. These findings indicate that aberrations of the Wnt signaling pathway may perform a crucial role in the development and differentiation status of the odontogenic epithelium in COCs via the deregulation of cell proliferation.