Expression of spindle assembly checkpoint proteins BubR1 and Mad2 expression as potential biomarkers of malignant transformation of oral leukoplakia: an observational cohort study

• Luís Monteiro ^[2] ; Patrícia Silva ^[3] ; Leonor Delgado ^[3] ; Barbas Amaral ^[4] ; Fernanda Garcês ^[3] ; Filomena Salazar ^[2] ; José Júlio Pacheco ^[2] ; Carlos Lopes ^[5] ; Hassan Bousbaa ^[6] ; Saman Warnakulasuriya ^[1]
  1. [1] King's College London

     King's College London

     Reino Unido

     
  2. [2] UNIPRO – Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Medicine and Oral Surgery Department, Instituto Universitário de Ciências da Saúde, Gandra, Portugal
  3. [3] UNIPRO – Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal
  4. [4] UNIPRO – Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Medicine and Oral Surgery Department, Instituto Universitário de Ciências da Saúde, Gandra, Portugal; Stomatology Department, Hospital de Santo António, Oporto Hospitalar Centre, Porto, Portugal
  5. [5] UNIPRO – Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Molecular Pathology and Immunology Department, Institute of Biomedical Sciences Abel Salazar (ICBAS), Porto University, Porto, Portugal
  6. [6] UNIPRO – Oral Pathology and Rehabilitation Research Unit, University Institute of Health Sciences (IUCS), CESPU, CRL, Gandra, Portugal; Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Universidade do Porto, Porto, Portugal

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• Localización: Medicina oral, patología oral y cirugía bucal. Ed. inglesa, ISSN-e 1698-6946, Vol. 26, Nº. 6 (November), 2021
• Idioma: inglés
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• Resumen

  • The Spindle Assembly Checkpoint (SAC) is a surveillance mechanism essential to ensure the accuracy of chromosome segregation during mitosis. Our aim was to evaluate the expression of SAC proteins in oral carcinogenesis, and to assess their potential in predicting malignant transformation of oral leukoplakia.

    We analysed the immunoexpression of BubR1, Mad2, Bub3, and Spindly proteins in 64 oral biopsies from 52 oral leukoplakias and 12 normal tissues. Univariate and multivariate analysis were performed to evaluate predictive factors for malignant transformation (MT).

    We observed that BubR1 and Mad2 were more highly expressed in high dysplasia grade lesions than in low grade or normal tissues (P<0.05). High expression of Spindly was significantly correlated with a high Ki-67 score (P=0.004). Six (11.5%) oral leukoplakias underwent malignant transformation. In univariate analysis, the binary dysplasia grade (high grade) (P<0.001) was associated with a higher risk of malignant transformation as well as high BubR1 (P<0.001) and high Mad2 (P=0.013) expression. In multivariate analysis, high expression of BubR1 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).

    Our findings reveal that BubR1 and Mad2 were associated with an increased risk for malignant transformation independently of histological grade and could be potential and useful predictive risk markers of malignant transformation in oral leukoplakias.