Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study / Expresión de las proteínas del punto de control del ensamblaje del huso BubR1 y Mad2 expresión como posibles biomarcadores de transformación maligna de la boca leucoplasia: un estudio de cohorte observacional

ABSTRACT

Background: The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the ac-curacy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oralcarcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia.Material and Methods: We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were per-formed to evaluate predictive factors for malignant transformation (MT).Results: We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than inlow grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki-67score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, thebinary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation aswell as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression ofBubR1 and Mad2 when combined showed an increased risk for malignant transformation (P=0.013; HR of 4.6,95% CI of 1.4-15.1). Conclusions: Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant trans-formation independently of histological grade and could be potential and useful predictive risk markers of malignanttransformation in oral leukoplakias.(AU)