Prognostic significance of p34cdc2 cyclin-dependent kinase and MIB1 overexpression, and HER-2/neu gene amplification detected by fluorescence in situ hybridization in breast cancer

Am J Clin Pathol. 1999 Oct;112(4):459-69. doi: 10.1093/ajcp/112.4.459.


The HER-2/neu oncogene, localized to chromosome 17q, shares substantial homology with the epidermal growth factor receptor. HER-2/neu gene amplification and protein overexpression have been associated with poor prognosis in breast cancer. Formalin-fixed paraffin-embedded primary invasive breast cancer tissues from 135 women were tested for HER-2/neu gene amplification by automated fluorescence in situ hybridization (FISH) using a sequence probe. The tumors also were evaluated by immunohistochemistry for proliferation markers Ki 67 (MIB1) and p34cdc2 cyclin-dependent kinase. Patients were followed up for a mean of 61 months. There were 70 node-negative and 65 node-positive cases. Ki 67 and p34cdc2 proliferation marker overexpression, HER-2/neu oncogene amplification, large tumor size, high tumor grade, advanced tumor stage, positive lymph node status, and distant metastasis at the time of diagnosis predicted disease-related death in combined node-negative and node-positive breast cancer. HER-2/neu gene amplification, tumor stage, lymph node metastasis, tumor grade, and distant metastasis at the time of diagnosis independently predicted disease outcome. HER-2/neu amplification detected by FISH also predicted disease-related death independent of lymph node status, tumor grade, and distant metastasis in breast cancer patients who received adjuvant therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / genetics
  • CDC2 Protein Kinase / analysis*
  • CDC2 Protein Kinase / genetics
  • Female
  • Gene Amplification*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Ki-67 Antigen / analysis*
  • Ki-67 Antigen / genetics
  • Lymph Nodes / pathology
  • Middle Aged
  • Nuclear Proteins / chemistry*
  • Nuclear Proteins / genetics
  • Prognosis
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-2 / genetics
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis


  • Antigens, Nuclear
  • Ki-67 Antigen
  • Nuclear Proteins
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2
  • CDC2 Protein Kinase