Amplification ofcyclin D1andMDM-2in oesophageal carcinoma

• Published in: European journal of surgical oncology Vol. 25; no. 4; pp. 364 - 367
• Main Authors: Morgan, R.J., Newcomb, P.V., Hardwick, R.H., Alderson, D.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.08.1999
• Subjects: blotting, Southern; gene amplification; immunohistochemistry; oesophageal neoplasms; oesophageal neoplasms; immunohistochemistry; blotting, Southern; gene amplification
• ISSN: 0748-7983; 1532-2157
• DOI: 10.1053/ejso.1999.0658

Aims:This study investigated amplification of thecyclin D1andMDM-2genes, and overexpression of the cyclin D1 gene product, in oesophageal carcinoma.Methods:Paired tumour and normal DNA samples from 26 oesophageal adenocarcinomas and 19 squamous cell carcinomas were analysed by Southern blotting with specific DNA probes forcyclin D1andMDM-2, and for a control gene (α-lactalbumin). Thecyclin D1andMDM-2gene copy numbers were calculated for each tumour. Expression of thecyclin D1gene was assessed by immunohistochemical analysis of its protein product.Results:Cyclin D1 gene amplification (by a factor of between two and six) was identified in seven tumours (16%).MDM-2gene amplification (by a factor 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 with early T stage (P=0.01; Fisher's exact test).Conclusions:Cyclin D1 andMDM-2amplification and cyclin D1 overexpression occur, although infrequently, in the development of oesophageal carcinoma. Cyclin D1 overexpression may influence tumour behaviour, causing the disease to present at an earlier T stage. The mechanism for this effect is unclear, and warrants further investigation.