Assessment of protein expression and gene status of human epidermal growth factor receptor (HER) family molecules in ameloblastomas

Authors

  • Mariko Oikawa,

    Corresponding author
    • Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
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  • Yasuhiro Miki,

    1. Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
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  • Yoshinaka Shimizu,

    1. Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
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  • Hiroyuki Kumamoto

    1. Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, Sendai, Japan
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Correspondence: Mariko Oikawa, Division of Oral Pathology, Department of Oral Medicine and Surgery, Tohoku University Graduate School of Dentistry, 4­1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan. Tel: +81 227178303; Fax: +81 227178304; E-mail: mariko-oikawa@dent.tohoku.ac.jp

Abstract

Background

To evaluate roles of human epidermal growth factor receptor (HER) family molecules in ameloblastomas, protein expression and gene status were analyzed in odontogenic tissues.

Methods

Sixty five ameloblastomas, 10 dental follicles, and 11 dentigerous cysts were immunohistochemically examined with antibodies against epidermal growth factor receptor (EGFR) and HER2, HER3, and HER4. Amplification of EGFR and HER2 was evaluated by chromogenic in situ hybridization (CISH). In 18 ameloblastomas, EGFR exons 19 and 21 were analyzed by direct DNA sequencing.

Results

Immunohistochemical reactivity for EGFR and HER2, HER3, and HER4 was detected in odontogenic epithelium. Expression of EGFR and HER4 was remarkable in these odontogenic tissues, as compared with that of HER2 and HER3. The level of HER2 immunoreactivity was significantly lower in ameloblastomas than in dental follicles and dentigerous cysts. Follicular ameloblastomas showed significantly higher expression of HER2 and HER4 than plexiform ameloblastomas. Reactivity for EGFR and HER3 was slightly stronger in recurrent ameloblastomas than in primary ameloblastomas. CISH did not reveal obvious amplification of EGFR or HER2 in ameloblastomas; however, EGFR and HER2 gene signals were significantly higher in follicular ameloblastomas than in plexiform ameloblastomas. Direct DNA sequencing of EGFR did not show any gene alteration in ameloblastomas.

Conclusion

Expression of HER family molecules, especially EGFR and HER4, in odontogenic tissues suggests that growth signals mediated by these receptor molecules contribute to cell proliferation, survival, and differentiation in both normal and neoplastic odontogenic epithelial tissues. Some of these molecules might be useful for predicting outcomes in patients with ameloblastomas.

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