Prognostic value of chromosomal imbalancies and the colon gene expression signatures in rectal cancer.

Abstract

465 Background: Some studies have suggested colon and rectal cancer as two different entities when considering DNA mutations or chromosomal imbalances. We therefore wondered if two colon gene expression signatures could predict specific survival. We also tested the influence of chromosomal imbalancies on prognosis in rectal cancer. Methods: Between 1998-2001 a series of 94 patients (pts) with rectal adenocarcinoma (T1-2-3 M0) were treated with preoperative radiotherapy (RT) with or without concurrent chemotherapy (CT) (78 pts) or with curative RT alone using contact X Ray therapy (CXRT) (18 pts). High-throughput analysis of genomic imbalancies and DNA expression were performed within the frame of the Carte d’Identité des Tumeurs (CIT) programme of Ligue du Cancer- France. Biostatistical analysis were performed and correlated with metastasis-free survival (MFS) and specific survival (SS). Coloprint and Oncotype DX colon signatures were tested on this cohort. Results: The median survival of the 96 patients was 105 months. The overall specific survival rate at 8 years was 75% for the preoperative group and 65 % for the RT alone group. Overall the rate of distant metastases was 30 % at 8 years (26 pts). A validated biopsy specimen was analysed in 67 pts for DNA expression and for genomic imbalances. Deletion of 8p and 1p36-35 correlated with MFS (p=0.001 and p=0.02 respectively) and SS (p=0.0002 and p=0.008 respectively). Multivariate analysis identified -8p as an independent prognostic factor of MFS (p=0.004) and SS (p=0.003). Validation of this deletion on an independent cohort is on-going. Regarding mRNA profile analysis, no stable consensus could identify clusters that accurately separate patients of bad and good SS or MFS, whatever the method used (28 methods of clustering). Coloprint signature could discriminate patients with the worst prognosis (SS: p<0.05) whereas Oncotype DX colon signature did not (SS: p=0.4). Conclusions: By analysing this series of patients from a single center we have been able for the first time in rectal cancer to identify -8p as an independent prognostic factor of MFS and SS. mRNA analysis suggest that colon and rectal cancer may not always share the same DNA expression profile.