EXPRESSION OF CYCLIN D1 AND EMS1 IN BLADDER-TUMORS - RELATIONSHIP WITH CHROMOSOME 11Q13 AMPLIFICATION

11q13 amplifications have been found in several cancers, including bla dder tumours,However, the biological significance of this genetic alte ration is not yet fully understood, To get more insight into the role of 11q13 amplification in bladder tumour development, we have studied the level of amplification and expression of 4 (protoonco)genes lying within the amplicon: cyclin D1, FGF3, FGF4 and EMS1 DNA amplification was found in 5/46 tumours, There was no correlation between amplificat ion and clinico-pathological data. No expression of FGF3 and FGF4 was detected whereas both cyclin D1 and EMS1 were expressed at higher leve l in tumours with amplifications, Thus cyclin D1 and EMS1, but not FGF 3 and FGF4, are likely to play a pathogenic role in the 11q13 amplific ation in bladder cancer, However, amplification is not the unique way of activation of these genes, Indeed, in situ hybridisation and Northe rn blot analysis have shown that most bladder tumours have a fair to h igh expression of cyclin D1 and EMS1 in contrast to normal urothelium with a moderate expression, Interestingly, a trend towards higher expr ession occurs in superficial versus invasive tumours (8.8+/-2.0 versus 1.9+/-0.4; P approximate to 13% for cyclin D1 and 4.5 +/- 1.4 versus 2.0 +/- 0.4; P approximate to 8% for EMS1), Moreover, the 9 tumours wi th low expression are all highly malignant, leading to the hypothesis that the tumours developing through a cyclin D1/EMS1 independent pathw ay are more aggressive.