Immunohistochemical analysis reveals a tumour suppressor-like role for the transcription factor AP-2 in invasive breast cancer

J Pathol. 1999 Dec;189(4):514-20. doi: 10.1002/(SICI)1096-9896(199912)189:4<514::AID-PATH463>3.0.CO;2-9.

Abstract

This paper describes the generation and characterization of a monoclonal antibody specific for two members of the AP-2 family of transcription factors, AP-2alpha and AP-2beta, and its subsequent application to archival primary breast tumour material. Nuclear localization of AP-2 was found in all expressing cases, but in general levels of immunostaining were low, with only 17 per cent of the 86 tumours examined showing very high expression levels. Nevertheless, data analysis of the whole patient series allowed the identification of significant relationships between levels of AP-2 and other important breast markers. Thus, expression of AP-2alpha/beta was found to correlate significantly with expression of both ER ( p=0.036*) and the universal cell-cycle inhibitor p21(cip) ( p=0.03*), but was inversely related to levels of the proto-oncogene ErbB2 ( p=0.008*). AP-2-positive tumours also showed a low rate of proliferation, with significantly reduced mitotic count and a lower tumour grade. There was no significant relationship with clinical parameters, but samples with adjacent normal tissue indicated that loss of the AP-2 marker was associated with disease progression from normal breast through to invasive disease. This was confirmed by examining separate series of pure normal and pure DCIS samples, both of which expressed significantly higher levels of AP-2 ( p=0.0001* in each case) than the invasive tumours. Overall, these findings implicate AP-2alpha/beta as having a role akin to that of a tumour suppressor in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal
  • Blotting, Western
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Nucleus / chemistry
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / analysis
  • DNA-Binding Proteins / analysis*
  • DNA-Binding Proteins / genetics*
  • Enzyme Inhibitors / analysis
  • Female
  • Genes, Tumor Suppressor*
  • Humans
  • Immunohistochemistry
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / genetics*
  • Receptor, ErbB-2 / analysis
  • Statistics, Nonparametric
  • Transcription Factor AP-2
  • Transcription Factors / analysis*
  • Transcription Factors / genetics*

Substances

  • Antibodies, Monoclonal
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Neoplasm Proteins
  • TFAP2A protein, human
  • TFAP2B protein, human
  • Transcription Factor AP-2
  • Transcription Factors
  • Receptor, ErbB-2