Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma

Aims: This study investigated amplification of the cyclin DI and MDM-2 gene s, and overexpression of the cyclin D1 gene product, in oesophageal carcino ma. Methods: Paired tumour and normal DNA samples from 26 oesophageal adenocarc inomas and 19 squamous cell carcinomas were analysed by Southern blotting w ith specific DMA probes for cyclin DI and MDM-2, and for a control gene (al pha-lactalbumin). The cyclin D1 and MDM-2 gene copy numbers were calculated for each tumour. Expression of the cyclin D1 gene was assessed by immunohi stochemical analysis of its protein product. Results: Cyclin DI gene amplification (by a factor of between two and six) was identified in seven tumours (16%). MDM-2 gene amplification (by a facto r of between two and 11) was identified in 10 tumours (22%). Overexpression of cyclin D1 protein was identified in eight tumours and was significantly associated with gene amplification (P = 0.04; Fisher's exact test), and wi th early T stage (P = 0.01; Fisher's exact test). Conclusions: Cyclin DI and MDM-2 amplification and cyclin D1 overexpression occur, although infrequently, in the development of oesophageal carcinoma. Cyclin D1 overexpression may influence tumour behaviour, causing the disea se to present at an earlier T stage. The mechanism for this effect is uncle ar, and warrants further investigation.