ORIGINAL ARTICLES

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

K Evangelou¹, A Kotsinas¹, T Mariolis-Sapsakos¹, A Giannopoulos², P K Tsantoulis¹, C Constantinides³, T G Troupis⁴, M Salmas⁴, A Kyroudis¹, C Kittas¹ and V G Gorgoulis¹

¹ Molecular Carcinogenesis Group, Department of Histology and Embryology, School of Medicine, University of Athens, Greece
² 1st Department of Surgery, School of Medicine, University of Athens, "Laikon" Hospital, Athens, Greece
³ 1st Department of Urology, School of Medicine, University of Athens, "Laikon" Hospital, Athens, Greece
⁴ Department of Anatomy, School of Medicine, University of Athens, Greece

Correspondence to:
Vassilis G Gorgoulis, Antaiou 53 Str., Lamprini, Ano Patissia 111 46, Athens, Greece; histoclub{at}ath.forthnet.gr

Background: E2F-1 expression is positively associated with tumour growth in oesophageal squamous-cell carcinomas (OSCC), while it exhibits oncosuppressive features in colonic adenocarcinomas (AC). To date there are no data regarding E2F-1 expression and its relationship with tumour kinetics (proliferation, apoptosis) in adenocarcinomas that develop on Barrett oesophagus.

Aim: As oesophageal adenocarcinomas occur almost exclusively in the metaplastic Barrett epithelium and the opposing E2F-1 behaviour seems to be cell and tissue-type dependent, we examined the manner in which E2F-1 acts in ACs of Barrett oesophagus.

Methods: We estimated the immunohistochemical expression of E2F-1, Ki-67, caspase-3 and p53 immunohistochemical status in 35 Barrett 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 oesophagus. Additionally, E2F-1 immunohistochemical status correlated positively with patient survival. These findings are opposite from those seen in OSCCs, suggesting that the tumour-suppressing E2F-1 behaviour in oesophageal adenocarcinomas is possibly due to the intestinal-type nature of the metaplastic Barrett mucosa.

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