Amplification of cyclin D1 and MDM-2 in oesophageal carcinoma.
OBJECTIVE
This study investigated amplification of the cyclin D1 and MDM-2 genes, 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 for cyclin D1 and MDM-2, and for a control gene (alpha-lactalbumin). The cyclin D1 and MDM-2 gene copy numbers were calculated for each tumour. Expression of the cyclin D1 gene 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-2 gene 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 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 disease to present at an earlier T stage. The mechanism for this effect is unclear, and warrants further investigation.
University Department of Surgery, Bristol Royal Infirmary, Bristol, BS2 8HW, UK.
R J
RJ
Morgan
P V
PV
Newcomb
R H
RH
Hardwick
D
D
Alderson
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D015139:Blotting, Southern; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism*; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051736:Proto-Oncogene Proteins c-mdm2; D015854:Up-Regulation
D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D019938:Cyclin D1; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2