Oncogenic Pathways in the Development of Oral Cancer

Abstract

Abnormality of EGFR gene and overexpression of the protein have been reported in various human tumors, with an abnormal amplification of the EGFR gene being reported in oral squamous cell carcinoma, although not limited to the final stages of the carcinogenic process. In fact, a low level of gene amplification also occurs at a significant frequency in epithelial dysplasia and carcinoma in situ, and, moreover, increased EGFR gene copies via amplification seems to play an important role in the development of invasive cancer [2]. Moreover, the expression of proliferation markers TGF-α and EGFR in cells of the oral epithelium presenting a spectrum of dysplastic changes revealed a serial upregulation both in terms of area and intensity of staining of TGF-α in the epithelial cells of oral precancerous lesions exhibiting features of dysplasia. Likewise, TGF-α expression has been reported higher than EGFR’s in the proliferative pool of the oral epithelium in oral precancer lesions, thus suggesting that an initial upregulation of TGF-α was likely to exert a paracrine effect on the adjacent nonproliferative cells therefore increasing the expression of the cell surface receptor [3]. Significant linear increase in the intensity of staining of EGFR in the differentiated cells of the stratum spinosum in oral leukoplakia with mild epithelial dysplasia has also been reported, which might be explained by the inducing role of TGF-α over DNA synthesis in noncycling cells [3].