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Int J Med Sci 2014; 11(9):971-978. doi:10.7150/ijms.9453

Research Paper

Wnt Signaling as a Possible Promoting Factor of Cell Differentiation in Pleomorphic Adenomas

Yukiko Okuda1,3, Keisuke Nakano1,4✉, Koji Suzuki2, Yoshihiko Sugita2,5, Katsutoshi Kubo2,5, Hatsuhiko Maeda2,5, Norimasa Okafuji6, Hiromasa Hasegawa1,4, Toshiyuki Kawakami1

1. Hard Tissue Pathology Unit, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri, Japan
2. Department of Oral Pathology, School of Dentistry, Aichi Gakuin University, Nagoya, Japan
3. Department of Oral and Maxillofacial Surgery, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Japan
4. Department of Oral Pathology, Matsumoto Dental University School of Dentistry, Shiojiri, Japan
5. Center for Advanced Oral Science, Aichi Gakuin University, Nagoya, Japan
6. Clinical Evaluation Unit, Matsumoto Dental University Graduate School of Oral Medicine, Shiojiri, Japan


There are well known that Wnt signaling was some roles of cell differentiation at the development tissues, especially the oral and maxillofacial regions of some developmental stages. Therefore, to determine Wnt signaling in the pleomorphic adenoma tissues, we examined. The expression of Wnt1 and β-catenin as well as the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30 cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost all tumor cells. The peripheral columnar cells in squamous metaplasia and small cuboidal cells in duct-like structures were strongly positive to Wnt1. Although β-catenin was clearly localized on the cell membrane of tumor cells, nuclear translocation was observed in small cuboidal cells and in some basaloid cells. The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests and small peripheral columnar cells forming duct-like structures. Moreover, among the three currently known Wnt pathways, β-catenin is the suggested pathway working during cell differentiation. Furthermore, peripheral columnar cells in solid tumor nests and in squamous metaplasia are governed by another Wnt pathway other than β-catenin. Therefore, Wnt signaling through β-catenin pathway may be involved in the 'mixed' differentiation characteristic of pleomorphic adenoma although another pathway may also be possibly working in other parts of the tumor tissue.

Keywords: pleomorphic adenoma, Wnt signaling, β-catenin, cytokeratin, immunohistochemistry, cell differentiation

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How to cite this article:
Okuda Y, Nakano K, Suzuki K, Sugita Y, Kubo K, Maeda H, Okafuji N, Hasegawa H, Kawakami T. Wnt Signaling as a Possible Promoting Factor of Cell Differentiation in Pleomorphic Adenomas. Int J Med Sci 2014; 11(9):971-978. doi:10.7150/ijms.9453. Available from