Abstract 586: Nuclear translocation of EGFR in ameloblastomas

Abstract

Abstract Ameloblastoma is a locally destructive and invasive tumour that can recur despite adequate surgical removal. Growth factors and their receptors play a key role in the growth of normal tissues and the development and progression of human neoplasms. Epidermal growth factor (EGF), a peptide growth hormone widely spread in human tissues, regulates proliferation of both normal and neoplastic cells. Increased expression or activity of EGFR has been shown in various cancers and in head and neck squamous cell carcinomas it is overexpressed in more than 90% of cases, emerging as a therapeutic target. The inhibition of EGFR has recently been suggested as a treatment option for ameloblastomas. Despite intense efforts that have been made to inhibit the activity of EGFR and HER2, most tumors do not respond well to treatment, and those that initially respond well after a time become resistant. Evidence shows a new pathway of EGFR activation, which activates the nuclear translocation of EGFR gene expression and other cellular processes. Upon signal activation, EGFR accumulates in the nucleus facilitated by binding with transcription factors E2F1 and STAT3 through importins, leading to up-regulation of B-Myb, iNos and cyclin D1. However, this nuclear translocation has not yet been investigated in ameloblastomas. The purpose of the present study was to investigate the EGFR nuclear translocation in encapsulated (unicystic) and infiltrative (multicystic) ameloblastomas using immunofluorescence analyzed by confocal microscopic. Eleven formalin-fixed and paraffin-embedded ameloblastoma samples were included in the study (n = 8 multicystic and n = 3 unicystic). EGFR nuclear translocation was assessed by using immunofluorescence followed by confocal microscopic analysis, after double staining with a mouse monoclonal anti-EGFR antibody (clone 8G6.2)/rabbit polyclonal to lamin B1. To assess colocalization of nuclear EGFR and cyclin D1, we performed double staining with a mouse monoclonal anti-EGFR antibody and rabbit monoclonal anti-cyclin D1. Inflammatory fibrous hyperplasia and oral squamous cell carcinoma were used for comparison. Our results showed that ten cases of ameloblastoma exhibited nuclear translocation. This positive staining was observed in the ameloblast-like cells. The EGFR nuclear translocation was also observed in oral squamous cell carcinoma and in the epithelium of inflammatory fibrous hyperplasia. In addition, nuclear EGFR colocalized with cyclin D1 in ameloblastomas. In conclusion, our study suggests that nuclear translocation of EGFR plays an important role in ameloblastoma pathogenesis and it may be associated with cell proliferation. Note: This abstract was not presented at the meeting. Citation Format: Núbia B. Pereira, Carolina C. Gomes, Ana Carolina de M. do Carmo, Marina G. Diniz, Dawidson A. Gomes, Ricardo S. Gomez. Nuclear translocation of EGFR in ameloblastomas. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 586. doi:10.1158/1538-7445.AM2015-586