Clinicopathologic significance of BubR1 and Mad2 overexpression in oral cancer


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Abstract

OBJECTIVES:BubR1 and Mad2 are central components of the mitotic checkpoint complex that inhibits anaphase onset until all chromosomes are correctly aligned at the metaphase plate. We propose to analyse the combined expression of BubR1 and Mad2 and assess its significance to oral squamous cell carcinoma (OSCC) diagnosis and prognosis.MATERIALS AND METHODS:BubR1 and Mad2 expression was assessed by real-time PCR in OSCC cell lines and in normal human oral keratinocytes, and by immunohistochemistry in 65 patients with OSCC. The results were compared regarding clinicopathological parameters, proliferative activity and survival.RESULTS:BubR1 and Mad2 transcripts were overexpressed in OSCC cell lines which also exhibited attenuated spindle assembly checkpoint activity. BubR1 and Mad2 were also overexpressed in patients with OSCC. BubR1 expression was associated with advanced stages and larger tumour size in univariate analysis, and with shorter overall survival both in univariate and multivariate analysis. Mad2 overexpression was associated with that of BubR1 and, importantly, high expression of Mad2 and BubR1 was associated with increased cellular proliferation.CONCLUSION:Our data propose a role for BubR1 and Mad2 in OSCC cellular proliferation, progression and prognosis.

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