Prognostic significance of Cyclin D1 (CCND1) amplification in adenocarcinoma of the esophagus

2007 
1957 Introduction: Cyclin D1 (CCND1) overexpression has been frequently reported in esophageal cancer. In other tumor entities, including pancreatic cancer, breast cancer, bladder and colon cancer CCND1 overexpression has been linked to gene amplification. The aim of our study was to analyze CCND1 copy number alteration in a large set of esophageal cancers with clinical follow up data. Materials and Methods: A total of 279 esophageal cancer samples on a tissue microarray (TMA), including 121 adenocarcinomas (ADC) and 158 squamous cell cancers (SQCC) and 141 matched metastases were analyzed for CCND1 gene alteration by means of fluorescence in situ hybridization (FISH). Amplification was defined as presence of at least two times more gene signals than centromer 11 signals. Results: Amplification was typically high level with more than 10 gene copies per tumor cell and was strikingly more frequent in squamous cell cancer (85/158, 54%) as compared to adenocarcinoma (14/121, 12%, P Conclusions: In conclusion, our data suggest that CCND1 amplification is of major clinical impact in esophageal cancer. This has not been reported for squamous cell cancer from other localizations. Squamous cell cancer of the esophagus is characterized by a molecular pathway involving CCND1 amplification. The overall adverse prognosis of squamous cell cancer of the esophagus might be directly linked to CCND1, since presence of amplification was linked to reduced survival also in adenocarcinoma of the esophagus.
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