p53 expression in altered limbal basal cells of pingueculae, pterygia, and limbal tumors

Purpose. We previously discovered that the pathogenesis of pterygia was due to a vimentin-expressing, altered limbal epithelial basal cell, the pterygium cell. Since UV radiation epidemiologically correlates as the etiologic agent for pterygia and limbal tumors and is mutagenic for the p53 gene, our goal was to search for p53 gene mutations immunohistochemically in the altered limbal basal cells of these growths and of pingueculae from which they seem to originate. Methods. Longitudinal serial sections through six pingueculae, 14 primary and five recurrent pterygia, and five limbal tumors were studied immunohistochemically with p53 monoclonal antibody DO-1 and, in some specimens, with antivimentin antibody. Results. P53 expression was found in the limbal cells of all pterygia, limbal tumors, and Stage II pingueculae, but not in normal limbal-corneal epithelial cells. However, when the same specimens were examined with a TUNEL assay, few if any apoptotic cells were found. A finding of increased nuclear p53 gene product with little or no apoptosis is consistent with an activating mutation of the p53 gene, resulting in increased steady-state levels of the protein. Conclusions. The finding of increased nuclear p53 in the limbal epithelium of pterygia, limbal tumors, and most pingueculae indicates the probable existence of p53 mutations in these cells as an early event in their development, which is consistent with their causation by UV radiation causation. In addition, due to a damaged p53-dependent programmed cell death mechanism, mutations in other genes are progressively acquired which allows the multi-step development of pterygia and limbal tumor cells from p53 positive cells overlying a Stage II pinguecula. Similarly, a pterygium dysplasia could arise from a pterygium cell. A classification for limbal basal cell tumors is proposed, and the different stromal changes in pingueculae, pterygia, and limbal tumors are identified. Two cell types were also identified: a p53-positive pinguecula limbal epithelial cell (a pinguecula II cell) and a p53-positive pterygium dysplasia cell (pterygium dysplasia cell).