Decreased expression of p63 in oral lichen planus and graft-vs.-host disease associated with oral inflammation

Abstract

Oral lichen planus (OLP) and graft-vs.-host disease (GVHD) are conditions with increased risk of malignant transformation to squamous cell carcinoma of the head and neck (SCCHN). The p63 gene encodes six different proteins and is expressed at high levels in SCCHN. Biopsies from patients diagnosed with OLP and GVHD were analysed for p63 protein expression using antibodies distinguishing between the major isoforms expressed in normal epithelia, in parallel with biopsies from normal buccal mucosa and SCCHN. In OLP and GVHD a decreased expression of all p63 isoforms was seen, while expression of p53 protein was upregulated, compared with normal mucosa. In SCCHN, p63 was abundantly expressed and some tumours showed strong p53 staining, suggestive of p53 mutation. Decreased p63 and increased p53 expression in OLP and GVHD indicates a coordinated action of these two related proteins to protect the oral mucosae from the damaging effects of underlying inflammation. In SCCHN disruption of the TP53 gene and overrepresentation of certain p63 isoforms has been seen, indicating that this could lead to neoplastic transformation.