Nuclear cyclin D1 overexpression is a critical event associated with cell proliferation and invasive growth in gallbladder carcinogenesis

J Gastroenterol. 2000;35(2):142-9. doi: 10.1007/s005350050027.

Abstract

Cyclin D1 overexpression is remarkably frequent in several human carcinomas and is believed to be a critical event in oncogenesis. We examined cyclin D1 expression, p53 expression, and the Ki-67 labeling index by immunostaining in human gallbladder mucosa in conditions varying from normal to malignant tissue. We also examined K-ras codon 12 mutations in these tissues with a two-step polymerase chain reaction. Nuclear cyclin D1 overexpression was observed in 48% of carcinomas occurring independently of adenoma, but not in adenomas, carcinomas arising in adenomas, or nonneoplastic lesions. Cytoplasmic cyclin D1 overexpression was observed in about 15% of abnormal specimens, irrespective of the type of epithelial abnormality. Carcinomas showing nuclear cyclin D1 overexpression had significantly higher Ki-67 labeling indexes than those with no overexpression. Moderately to poorly differentiated adenocarcinomas showed a higher incidence of nuclear cyclin D1 overexpression than papillary to well differentiated carcinomas. Specimens with cyclin D1 overexpression showed a high incidence of lymph permeation, venous permeation, and lymph node metastasis. We conclude that nuclear cyclin D1 overexpression is a critical event importantly associated with cell proliferation and invasive growth in gallbladder carcinogenesis, and that cyclin D1 immunostaining may become a useful marker for evaluating gallbladder carcinomas.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenoma / genetics
  • Adenoma / metabolism*
  • Adenoma / pathology
  • Biomarkers, Tumor
  • Cell Division
  • Cell Nucleus / metabolism*
  • Codon
  • Cyclin D1 / biosynthesis*
  • DNA, Neoplasm / analysis
  • Gallbladder Neoplasms / genetics
  • Gallbladder Neoplasms / metabolism*
  • Gallbladder Neoplasms / pathology
  • Genes, ras / genetics
  • Humans
  • Immunoenzyme Techniques
  • Ki-67 Antigen / metabolism
  • Point Mutation
  • Polymerase Chain Reaction
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / biosynthesis

Substances

  • Biomarkers, Tumor
  • Codon
  • DNA, Neoplasm
  • Ki-67 Antigen
  • Tumor Suppressor Protein p53
  • Cyclin D1