TP53 mutations, amplification of P63 and expression of cell cycle proteinsin squamous cell carcinoma of the oesophagus from a low incidence area in Western Europe

In Europe, high incidence rates of oesophageal squamous cell carcinoma (SCC E) are observed in western France (Normandy and Brittany) and in north-east ern Italy. Analysis of TP53 mutations in tumours from these regions has sho wn a high prevalence of mutations at A:T basepairs that may result from DNA damage caused by specific mutagens. However, the spectrum of TP53 mutation s in regions of low incidence is unknown. We report here TP53 mutation anal ysis in 33 SCCE collected in Lyon, an area of low incidence. These tumours were also examined for MDM2 and P63 amplification, and for expression of p1 6(INK4a/CDKN2a), cyclin E, p27(Kipl) and Cox2. TP53 mutations were detected in 36% of the cases (12/33). In contrast with regions of high incidence, t he mutation spectrum did not show a high prevalence of mutations at A:T bas e pairs. P63 was amplified in 5/32 cases tested (15.5%). No amplification o f MDM2 was found. Expression studies revealed frequent loss of p16(INK4a/CD KN2a) (46%) and p27(Kipl) (25%) expression, and frequent overexpression of Cyclin E (70%) and Cox2 (42%). Overall, these results indicate that in Euro pe, SCCE from areas of high and low incidence present a similar pattern of molecular alterations but differ by the type of TP53 mutations. (C) 2001 Ca ncer Research Campaign.