MAD2 expression in oral squamous cell carcinoma and its relationship to tumor grade and proliferation

Anticancer Res. 2014 Dec;34(12):7021-7.

Abstract

Background: Defects in the cell-cycle surveillance mechanism, called the spindle checkpoint, might contribute to the chromosomal instability observed in human cancers, including oral squamous cell carcinoma. MAD2 and BUBR1 are key components of the spindle checkpoint, whose role in oral carcinogenesis and clinical relevance still need to be elucidated.

Materials and methods: We analyzed the expression of MAD2 in 49 cases of oral squamous cell carcinoma by immunohistochemistry and compared the findings with clinicopathological parameters, proliferative activity, BUBR1 expression and DNA ploidy.

Results: MAD2 was over-expressed in 18 (36.7%) cases. Tumors with over-expression of MAD2 were associated with the progression of histological grade from well to poor differentiation (p<0.001), the extent of lymph nodes involvement (PN) (p=0.0339) and Ki-67 labeling index (p<0.001).

Conclusion: MAD2 may be involved in oral carcinogenesis and may represent an important prognostic factor associated with a more malignant phenotype of oral squamous cell carcinoma.

Keywords: BUBR1; MAD2; Squamous cell carcinoma; oral; prognostic factor; spindle checkpoint.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / biosynthesis*
  • Biomarkers, Tumor / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Cell Proliferation
  • Chromosomal Instability / genetics
  • Disease Progression
  • Female
  • Humans
  • Lymphatic Metastasis
  • M Phase Cell Cycle Checkpoints / genetics*
  • Mad2 Proteins / biosynthesis*
  • Mad2 Proteins / genetics
  • Male
  • Middle Aged
  • Mouth Neoplasms / metabolism
  • Mouth Neoplasms / pathology*
  • Neoplasm Grading
  • Prognosis
  • Protein Serine-Threonine Kinases / biosynthesis*
  • Protein Serine-Threonine Kinases / genetics
  • Tissue Fixation

Substances

  • Biomarkers, Tumor
  • MAD2L1 protein, human
  • Mad2 Proteins
  • BUB1 protein, human
  • Protein Serine-Threonine Kinases