Siriwardena B S M S, Kudo Y, Ogawa I, Tilakaratne W M, Takata T
Department of Oral Maxillofacial Pathobiology, Division of Frontier Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8553, Japan.
Oral Oncol. 2009 Feb;45(2):103-8. doi: 10.1016/j.oraloncology.2008.03.008. Epub 2008 May 16.
The Wnt pathway is involved in carcinogenesis and three regulatory genes of the Wnt pathway, APC (adenomatous polyposis coli), beta-catenin and Axin are frequently mutated in some primary human cancers. This study was conducted to clarify the relation of beta-catenin accumulation and the mutation of the CTNNB1 (beta-catenin) gene with the mutation of APC gene in the process of development of odontogenic tumors including ameloblastoma and odontogenic carcinoma (OC). beta-Catenin accumulation was examined by immunohistochemistry in formalin-fixed, paraffin-embedded samples of six ameloblastomas and eight OCs. We also performed a mutation analysis of CTNNB1 and APC to examine the cause of beta-catenin accumulation. All ameloblastoma cases and six out of eight (75%) OC cases exhibited beta-catenin accumulation in the nucleus. CTNNB1 mutation was only found in one OC case, whereas three of six (50%) ameloblastoma cases and two out of eight (25%) OC cases had APC mutations within the mutational cluster region. Our findings suggest that aberrant beta-catenin expression and APC missense mutation may play an important role for the pathogenesis of epithelial odontogenic tumors.
Wnt信号通路参与肿瘤发生，在一些原发性人类癌症中，Wnt信号通路的三个调控基因，即腺瘤性结肠息肉病基因（APC）、β-连环蛋白和轴抑制蛋白（Axin）经常发生突变。本研究旨在阐明在成釉细胞瘤和牙源性癌（OC）等牙源性肿瘤发生过程中，β-连环蛋白的积聚以及CTNNB1（β-连环蛋白）基因突变与APC基因突变之间的关系。通过免疫组织化学方法，对6例成釉细胞瘤和8例OC的福尔马林固定、石蜡包埋样本进行β-连环蛋白积聚检测。我们还对CTNNB1和APC进行了突变分析，以探究β-连环蛋白积聚的原因。所有成釉细胞瘤病例以及8例OC病例中的6例（75%）显示细胞核内有β-连环蛋白积聚。CTNNB1突变仅在1例OC病例中发现，而6例成釉细胞瘤病例中的3例（50%）以及8例OC病例中的2例（25%）在突变簇区域存在APC突变。我们的研究结果表明，异常的β-连环蛋白表达和APC错义突变可能在牙源性上皮肿瘤的发病机制中起重要作用。
