ID protein expression in oral epithelial dysplasia and squamous cell carcinoma

Abstract

Id proteins were recently described as antagonizing basic helix-loop-helix transcription factors, which ordinarily play a key role in cell development, proliferation, and differentiation. Thus, Id overexpression correlates with cell proliferation and arrested differentiation. Id expression has been observed in normal skin and overexpression in a variety of carcinomas, but no studies have examined its expression in the oral cavity. To evaluate the possible role of Id in oral carcinogenesis, we examined immunohistochemical staining patterns for Id-1, Id-2, and Id-3 on sections of “normal” oral mucosa (n = 5) and sections with mild/moderate dysplasia (n = 5), severe dysplasia/carcinoma in situ (n = 5), well/moderately differentiated squamous cell carcinoma (SCC; n = 5) and poorly differentiated SCC (n = 5). The presence of staining was evaluated in basal/parabasal (B/PB), lower spinous (LS), upper spinous (US), and stratum corneum epithelial layers. Staining was considered focal if <50% and diffuse if >50% of cells stained. Staining intensity was graded on a scale of 0 to 3. Id-1 staining was cytoplasmic; in all 5 cases of normal epithelium, it was diffuse in the B/PB layer (average intensity [AI] = 2). Two cases of normal epithelium also exhibited focal LS staining (AI = 0.8). Among cases of mild/moderate dysplasia, all had diffuse B/PB (AI = 2.6), 3 diffuse and 2 focal LS (AI = 3), and 2 focal US staining (AI = 0.4). Among cases of severe dysplasia/carcinoma in situ, all 5 had diffuse B/PB and LS staining and 4 exhibited diffuse US staining (AI = 2.4, 2.2, and 1.6). No trends were seen for Id-2 and Id-3, which stained all but the stratum corneum in both normal and dysplastic epithelium. In 7 of 10 cases of oral SCC, Id-1, Id-2, and Id-3 stained more than 67% of tumor cells, with an AI range of 1.75 to 2.80. Id-1 expression generally increases in upper levels of oral epithelium as the degree of dysplasia increases, and Id-1, Id-2, and Id-3 overexpression is seen in oral SCC. Future studies will examine Id expression as a potential prognostic indicator in oral dysplasia and SCC.