Immunohistochemical Study of DNA Topoisomerase Type II Alpha and Ki-67 in Oral Squamous Cell Carcinoma.

Abstract

DNA topoisomerase type II alpha (Topo IIα) is a nuclear enzyme associated with cell proliferation and chemosensitivity/resistance in various neoplastic lesions. Topo IIα is expressed from the S phase of the cell cycle, peaking in the G2/M phases and decreasing to minimum levels during G0 and G1 phases. In the present study, we examined whether expression of Topo IIα could be reliably localized in proliferative cells in oral squamous cell carcinoma (OSCC), compared with Ki-67 expression in Ki-67 positive proliferative cells. Formalin-fixed, paraffin-embedded blocks of samples from 22 OSCC cases were used. Immunolocalization of Topo IIα and Ki-67 was examined in serial sections using a streptavidin-biotin complex-HRP system. Topo IIα was localized in the basal and parabasal layers in non-pathological squamous epithelium (NPSE). The localization of Topo IIα was perfectly consistent with Ki-67 expression. Also, in OSCC, the immunolocalization for Topo IIa was largely consistent with Ki-67. The labeling index (LI) in NPSE was 5.42±1.89 for Topo IIα and 10.58±3.73 for Ki-67. The LI in OSCC was 25.1±19.23 for Topo IIα and 42.57±20.96 for Ki-67. Significant differences were observed between NPSE and OSCC with regard to LI (P<0.005). In addition, a significant correlation was observed between Topo IIα-LI and Ki-67-LI in NPSE (γ=0.91, P<0.0001) and OSCC (γ=0.65, P<0.001). With regard to tumor differentiation, LIs in poorly differentiated tumor were significantly higher than those in well or moderately differentiated tumors (P<0.01). These findings indicate that expression of Topo IIα is closely associated with cell proliferation. This suggests that Topo IIα immunostaining offers a useful tool for the detection of proliferating cells in NPSE and OSCC.