Expression of BUB1 protein in gastric cancer correlates with the histological subtype, but not with DNA ploidy or microsatellite instability

J Pathol. 2004 Feb;202(2):208-14. doi: 10.1002/path.1499.


During mitosis, the spindle checkpoint delays the onset of anaphase until all chromosomes have attached properly to the mitotic spindle, preventing chromosome missegregation. BUB (budding uninhibited by benzimidazole) 1 is one of the key components of this checkpoint. BUB1 mutations are rare in cancer tissues and no mutations have been identified in gastric cancer. In mice, immunodepletion of BUB1 abolished the spindle checkpoint. Thus, aberrant expression of BUB1 protein could impair mitotic checkpoint function, resulting in aneuploidy, a common phenomenon in gastric cancer. In the present study, an antibody was generated against BUB1 and its expression was studied in gastric cancer tissue sections (n = 80) by immunohistochemistry. Nuclear BUB1 expression was found in all gastric cancer cases. The proportion of tumour cells expressing BUB1 was significantly greater in diffuse-type than in intestinal-type gastric carcinoma (p < 0.001). No correlation was found between BUB1 expression and deoxyribonucleic acid (DNA) ploidy, microsatellite instability or any other histopathological parameters investigated. To the authors' knowledge, this is the first study of BUB1 protein expression in gastric cancer tissues. Different BUB1 protein expression levels in intestinal- and diffuse-type gastric cancer may provide further evidence of a potential link between different genetic pathways and morphological phenotype in gastric carcinogenesis. However, further studies are needed to establish whether there is an association between BUB1 protein expression level and mitotic spindle checkpoint function in gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA, Neoplasm / analysis*
  • Disease Progression
  • Female
  • Gastric Mucosa / metabolism
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Microsatellite Repeats
  • Middle Aged
  • Neoplasm Proteins / immunology
  • Neoplasm Proteins / metabolism*
  • Ploidies
  • Protein Kinases / immunology
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Sensitivity and Specificity
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology


  • DNA, Neoplasm
  • Neoplasm Proteins
  • Protein Kinases
  • BUB1 protein, human
  • Bub1 protein, mouse
  • Bub1 spindle checkpoint protein
  • Protein-Serine-Threonine Kinases