Lichen sclerosus (LS) is an inflammatory disease of unknown aetiology and pathogenesis. It is a disorder of the skin, which is most common in the genital area but can occur anywhere on the body. It affects both sexes and all age groups. In a review by Meffert et al (1995) of 5207 patients, the female-to-male incidence was reported as 6:1, with genital involvement in 83% of cases. The majority of sufferers of anogenital LS are either middle-aged or elderly women. The predominant symptom in females is an intractable itch, which is often associated with dysuria, dyspareunia, dryness of the skin, labial stenosis or fusion and, in children, constipation (Laude et al, 1980).
There have been many studies assessing the risk of squamous cell carcinoma of the vulva (SCC) in inflammatory diseases of the vulva. Wallace (1971) reported that 12 of 290 (4%) patients developed SCC following a history of LS during a 12-year period but further follow-up studies have shown a wide range of risk of progression (Hart et al, 1975; Meffert et al, 1995; Carlson et al, 1998). Others (Rueda et al, 1994; Scurry et al, 1997; Vilmer et al, 2000) have looked at the skin adjacent to SCC which, not uncommonly, shows epithelial disorders; the most common are LS and squamous hyperplasia (SH).
The TP53 gene is located on chromosome 17p13.1; it consists of 11 exons with 10 introns. Exon 1 is noncoding, while exons 5–8 are part of the highly evolutionarily conserved domain. Mutations in the TP53 gene are the most frequent genetic changes in human cancers, and the spectrum of mutations can indicate tumour aetiology and molecular pathogenesis (Levine et al, 1991; Greenblatt et al, 1994). In addition, a comparison of the mutation profile between malignant and potential premalignant lesions can give an indication of the clonality and progression of such tumours.
The aim of this study was to assess the presence of TP53 mutations in SCC and the adjacent non-neoplastic epithelial disorders of the vulva (LS and SH; NNEDV) and to compare the results of the mutation analysis with immunohistochemsitry (IHC) results. It was hoped that the data would also provide information on the clonality of SCC and the carcinogenic progression of adjacent lesions.