A70
Can DNA repair proteins be used as molecular markers of survival in oesophageal cancer?
Richard Gillies1, Michal Presz2, Rachel Waters3, Rebecca Harrison2, Mark Middleton1, Janusz Jankowski4
1Oxford Cancer Centre, UK, 2Gastrointestinal Prevention Group, University of Oxford, UK, 3Centre for Statistics in Medicine, University of Oxford, UK, 4Digestive Disease Centre, Leicester Royal Infirmary, UK
Background
Traditional predictors of survival in oesophageal cancer patients include TNM stage and resection margin status. Although these may accurately predict survival for groups of patients, individuals within the same disease stage exhibit very different outcomes, prompting a search for molecular markers that provide additional survival information. Previous studies have suggested a possible association between survival in oesophageal cancer and expression of DNA repair proteins, such as ERCC1, a member of the nucleotide excision repair pathway.
Aim
To determine whether nuclear expression of DNA repair proteins in oesophageal cancer tissue are associated with survival in patients undergoing definitive surgery.
Method
Tissue samples were obtained from 100 patients with oesophageal adenocarcinoma who underwent resection with curative intent, and received no neo-adjuvant therapy. Nuclear expression of 4 DNA repair proteins, MRE11, ATM, XPF and XPA, was determined by immunohistochemistry as either absent, weak, moderate or strong. Patients were followed up for a minimum of seven years and survival analysis was performed using Kaplan-Meier plots and logrank testing.
Results
Nuclear expression of MRE11 was detected in 67% of oesophageal cancer tissue samples, ATM in 36% of samples, XPF in 87% of samples and XPA in 87% of samples. There was no significant association between overall survival and nuclear expression of MRE11 (logrank p=0.78), ATM (p=0.73), XPF (p=0.19) or XPA (p=0.96).
Conclusion
Despite previous studies suggesting a possible association between survival in oesophageal cancer and the expression of proteins involved in nucleotide excision repair, our study found no significant association between survival and the expression of 2 members of this pathway, XPF and XPA. In addition, we found no association between survival and the expression of 2 other DNA repair proteins. Our results suggest that immunohistochemical analysis of MRE11, ATM, XPF and XPA is unlikely to be helpful in describing prognosis in oesophageal cancer.
