Histone γ-H2AX as a possible biomarker in Barrett´s Esophagus disease progression

Barrett’s esophagus (BE) is an acquired preneoplastic condition that is characterized by replacement of a stratified squamous epithelium of the distal esophagus by a columnar epithelium. BE represents a permanent risk for developing esophageal adenocarcinoma (EAC). Thus, there is a strong need for specific molecular markers of BE progression that would enable early diagnosis of developing EAC. In our study we followed accumulation of ?-H2AX, a marker of the DNA damage response (DDR) pathway activation, together with expression of active β-catenin and two inflammatory cytokines, IL-8 and IL-1β. Our results show that the activation of the DDR in BE increases with disease progression and that ?-H2AX accumulates mainly in EAC. Active β-catenin is found in cytoplasm in all disease stages whereas its membrane localization is exclusively associated with EAC. While the level of IL-1β increased accordingly with tumor progression, IL-8 was expressed constitutively in all disease stages. We conclude that genetic alterations associated with premalignant stages of BE do not have capacity to evoke DDR and that ?-H2AX is a useful biomarker of disease progression of BE to EAC.