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(American Journal of Pathology. 2003;163:1707-1712.)
© 2003 American Society for Investigative Pathology

Short Communication

ß-Catenin Mutations Are Frequent in Calcifying Odontogenic Cysts, but Rare in Ameloblastomas

Shigeki Sekine^*, Sunao Sato, Takashi Takata, Yasuo Fukuda, Takeshi Ishida, Mitsunobu Kishino, Tatsuhiro Shibata^*, Yae Kanai^* and Setsuo Hirohashi^*

From the Pathology Division,^* National Cancer Center Research Institute, Tokyo; the Department of Oral Maxillofacial Pathobiology, Division of Frontier Medical Science, Hiroshima University, Hiroshima; Clinical Laboratory, Osaka University Dental Hospital, Suita; and the Department of Oral Pathology, Graduate School of Dentistry, Osaka University, Osaka, Japan

We have reported previously that alterations to ß-catenin occur frequently in adamantinomatous craniopharyngioma. Based on its histological resemblance to some odontogenic tumors, we suspected the presence of common genetic alterations among these tumors. To address this issue, 11 cases of calcifying odontogenic cyst (COC) and 20 cases of ameloblastoma were investigated for the presence of ß-catenin mutations and ß-catenin expression. Ten COCs were successfully analyzed by direct sequencing, and nine of them were found to harbor somatic ß-catenin mutations. Immunohistochemically, all of the COCs showed nuclear and cytoplasmic expression of ß-catenin with a heterogeneous pattern. No ß-catenin mutations were found in ameloblastomas, except for one case of the follicular type. All follicular ameloblastomas exhibited moderate nuclear and cytoplasmic accumulation of ß-catenin, in contrast to the predominantly membranous expression seen in the plexiform type. ß-Catenin mutation is considered to be a characteristic genetic feature of COC, and may play a critical role in its histogenesis. Although ameloblastoma closely resembles COC histologically, the two have genetically distinctive features.

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