E2F-1 overexpression correlates with decreased proliferation and better prognosis in adenocarcinomas of Barrett's oesophagus

Abstract

Backround: E2F-1 expression is positively associated with tumour growth in oesophageal squamous-cell carcinomas (ESCC), while it exhibits oncosuppressive features in colonic adenocarcinomas (AC). There are no data regarding E2F1 expression and its relationship with tumour kinetics (proliferation, apoptosis) in adenocarcinomas that develop on Barrett's oesophagus. Aims: As oesophageal adenocarcinomas occur almost exclusively in the metaplastic Barrett's epithelium and the opposing E2F-1 behaviour seems to be cell and tissue-type dependent, we examined in which manner E2F-1 acts in ACs of Barrett¢s oesophagus. Methods: We estimated the immunohistochemical expression of E2F-1, Ki-67, Caspase-3 and p53 status in 35 Barrett's oesophagus ACs. Results: E2F-1 immunopositivity correlated inversely with Ki-67, by semi-serial section and statistical analysis (p=0.023, Spearman correlation). Semi-serial section analysis revealed a direct association between E2F-1 and Caspase-3 staining. No correlation was found with p53 status. Cases with higher E2F-1 immunoexpression exhibited longer survival (p=0.047, Cox-regression). Conclusions: E2F-1 expression was negatively related to tumour-proliferation in ACs of Barrett's oesophagus. Additionally, E2F-1 immunohistochemical status correlated positively with patient's survival. These finding are opposite from that in ESCCs, suggesting that the tumour-suppressing E2F-1 behaviour in oesophageal adenocarcinomas is possibly due to the intestinal-type nature of the metaplastic Barrett's mucosa.