Epithelial p53 gene expression and mutational analysis, combined with growth fraction assessment, in oral lichen planus

Abstract

The immunohistochemical detection of epithelial p53 protein expression in oral lichen planus (OLP) biopsies was supplemented with molecular analysis for mutations of the p53 gene using the polymerase chain reaction ‐ single stranded conformational polymorphism (PCR‐SSCP) technique. p53 protein expression, in the basal epithelial cell layer, as detected by the DO7 and 1801 antibodies, was significantly more frequent in OLP compared with other oral keratoses and normal mucosa, as was the growth fraction. The 10 OLP biopsies that had the most frequent p53 staining (plus a case of OLP found in continuity with a SCC) were screened by the PCR‐SSCP technique, but no mutations were detected in the p53 gene (exons 5–9). The p53 overexpression in the OLP samples may be a physiological response to the hyper‐proliferative state, as revealed by the growth fraction determination. This may usefully serve to protect against mutagenesis, and so be a factor in the low incidence of carcinoma associated with OLP.

Oral lichen planus: controversies surrounding malignant transformation

“…The very few mutational analyses of the p53 gene in OLP have produced contradictory results. Whereas Ogmundsdottir et al (2002) observed mutation of this gene in 30% of OLP cases, Schifter et al (1998) detected no cases with this mutation. Our group (González‐Moles et al , 2006) and other authors (Dekker et al , 1997; Tanda et al , 2000) have proposed that the frequent overexpression of p53 largely corresponds to the wild type of the protein, which may act preferentially to halt the cell cycle for DNA repair.…”

“…Most studies on cell proliferation in OLP have reported a marked increase in the proliferation rate of basal epithelial cells (Maidhof et al , 1981; Schifter et al , 1998; da Silva Fonseca and do Carmo, 2001; Valente et al , 2001; Taniguchi et al , 2002; González‐Moles et al , 2006), and some authors have proposed that this might be an important event in the development of cancer in OLP (Taniguchi et al , 2002). Valente et al (2001) found that the cell proliferation rate, according to the ki‐67 expression, was significantly higher in OLP patients who developed cancer than in patients who did not.…”

“…Various researchers (Schifter et al , 1998; da Silva Fonseca and do Carmo, 2001; Valente et al , 2001; Taniguchi et al , 2002), including our group (Bascones‐Ilundain et al , 2005, 2006, 2007; González‐Moles et al , 2006), consider that the response of epithelial cells to intense T lymphocyte attack in OLP, with scarce apoptosis and increased cell proliferation, is aimed at preservation of the epithelial structure. Thus, if most attacked basal cells died of apoptosis, the result would be the loss of epithelial regenerative capacity and the appearance of erosive lesions, the most severe clinical situation in OLP.…”

Ultraviolet A within Sunlight Induces Mutations in the Epidermal Basal Layer of Engineered Human Skin

“…Exons 5 to 9 of p53 were initially amplified in all samples using the primers and cycling parameters described. 23,24 Negative controls without DNA were included in each PCR cycle. PCR cycles were performed in a Hybaid Px2 thermal cycler.…”

Expression of heme oxygenase‐1 in oral lichen planus

“…According to these studies, the proliferative activity of most epithelial cells is increased in OLP. Van Oijen et al suggest that cyclin D1, which is considered to be a cell growth stimulation factor, may overcome the inhibitory effect exerted by p21 in the oral mucosa 31 …”