Prediction of CCND1 amplification using plasma DNA as a prognostic marker in oesophageal squamous cell carcinoma

BACKGROUND: We aimed to develop a new biomarker to predict cyclin D1 (CCND1) status using plasma DNA in oesophageal squamous cell carcinoma (ESCC) patients. METHODS: We evaluated the ratio of the CCND1 (11q13) dosage to the dopamine receptor D2 (DRD2; 11q22-23) dosage (C/D ratio) as CCND1 copy number. This study was divided into three steps: (1) Determination of a cutoff value for the C/D ratio in test scale; (2) Comparison of the C/D ratio in between plasma samples and cancer tissues in ESCC patients showing high plasma C/D ratio; (3) Validation study of the clinical application of the plasma C/D ratio as a diagnostic and prognostic marker, by comparing with clinicopathologic factors in 96 ESCC patients. RESULTS: The plasma C/D ratio was significantly higher in the ESCC group than the controls (P = 0.0134). A high plasma C/D ratio reflected the tumour C/D ratio, and significantly correlated with a poorer prognosis (P = 0.0186). Moreover, the high C/D ratio was found to be an independent prognostic factor on multivariate analysis (P = 0.0266; hazard ratio 5.988). CONCLUSION: Prediction of CCND1 amplification using plasma DNA is thought to be a promising prognostic biomarker in ESCC patients. British Journal of Cancer (2010) 102, 1378-1383. doi:10.1038/sj.bjc.6605657 www.bjcancer.com Published online 13 April 2010 (C) 2010 Cancer Research UK