Expression of BUBR1 in human oral potentially malignant disorders and squamous cell carcinoma

Abstract

BUBR1 is one of the key components of the spindle assembly checkpoint (SAC) machinery and is activated in response to kinetochore tension. Defects in the SAC contribute to an increased rate of aneuploidization during tumorigenesis. The aim of the present study was to examine the immunohistochemical expression of BUBR1 protein for human oral squamous cell carcinogenesis. A total of 120 samples of squamous cell carcinoma (SCC, n = 43) and 5 types of potentially malignant disorders (PMDs: oral epithelial dysplasia, n = 11; hyperkeratosis/epithelial hyperplasia, n = 20; lichen planus, n = 16; submucous fibrosis, n = 19; and verrucous hyperplasia, n = 11) of human oral mucosa (1991-2001) from our institution were retrieved and immunohistochemical staining were performed. Normal oral mucosa (n = 9) and fibrous hyperplasia (n = 9) from patients without the aforementioned oral habits were also included in the study. BUBR1 staining was detected at the basal and suprabasal layers in 75 (97.4%) of 77 samples of PMD and 43 (100%) of 43 samples of SCC of oral mucosa but was absent in all samples of normal oral mucosa (n = 9) and fibrous hyperplasia (n = 9). BUBR1 expression of various types of PMD and SCC of oral mucosa was significantly overexpressed as compared respectively with normal mucosa (P < .001) and fibrous hyperplasia (P < .001). Moreover, the expression of oral SCC was significantly higher as compared respectively with the 5 types of oral PMD; on the other hand, BUBR1 expression of verrucous hyperplasia was significantly higher than that of the other 4 types of PMD of oral mucosa (P < .001). Our results may interpret that BUBR1 protein is suggested to be one of the contributing factors involved in the pathogenesis of oral SCC. These also hypothesize that BUBR1 protein is a putative biomarker for human oral squamous cell carcinogenesis.