Objectives: The ZEB family of transcription factors (ZEB1 and ZEB2) have been demonstrated to play a role in metastatic progression of several cancers, and may also influence the initial transformation and generation of cancer stem cells. However, the expression pattern of ZEB proteins in the development of oral squamous cell carcinoma has not been investigated. The purpose of this study was to define changes in expression and subcellular localization of the ZEB family in both precancerous lesions and different grades of OSCC. Materials and Methods: Seventy-nine tongue biopsies were subjected to immunohistochemistry and immunofluorescence to determine the expression and subcellular location of ZEB1 and ZEB2 across six histological grades of precancerous and cancerous lesions. Results: Surprisingly, Both ZEB1 and ZEB2 exhibit changes in subcellular location between healthy tissue, dysplasia, carcinoma in situ, and well differentiated, moderately differentiated, and poorly differentiated carcinoma. ZEB1 expression in healthy tissue is mainly nuclear. As carcinoma progresses, subsets of patients show either primarily cytosolic or primarily nuclear ZEB1 in tumors. In histologically normal tissue, ZEB2 is expressed in the cytosol of a band of suprabasal cells. In early grades of carcinoma it remains cytosolic, but in more advanced carcinoma becomes a mix of cells with either nuclear or cytosolic ZEB2. Conclusions: Changes of subcellular distribution of ZEB1 and ZEB2 occur during development of oral squamous cell carcinoma. Cytosolic localization of either ZEB1 or ZEB2 likely disrupts their ability to regulate transcription. The presence of patients with differences in ZEB1 or ZEB2 localization suggest that there may be different clinical outcomes related to different patterns of expression.
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Expression of ZEB factors in oral squamous cell carcinoma.
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