Since previous studies reported that genome instability is an early event during the progression of UC-related neoplasia (Willenbucher et al., 1999), we aimed to test whether the progression of UC was associated with genome instability, by evaluating the expression of S139-phosphorylation of histone H2Ax (γH2Ax), a sensitive marker of DSBs, using immunohistology. Here, H2AX is linked to neoplasm.