Expression of activator protein 2 in prostate cancer is related to tumor differentiation and cell proliferation

Eur Urol. 2000 May;37(5):573-8. doi: 10.1159/000020195.

Abstract

Objectives: Activator protein 2 (AP-2) is a DNA-binding transcription factor that can activate the expression of p21 (waf1/cip1), which in turn causes growth arrest of cells through inhibition of cyclin-dependent kinases required in G1-S progression. The aims of the present study were to analyze the expression of AP-2 in prostate cancer and to relate the results of AP-2 immunohistochemistry to other known prognostic factors and patient survival.

Methods: AP-2alpha was demonstrated by an immunohistochemical method in 215 prostate cancer cases, and the results of immunohistochemistry were related to other known prognostic factors and patient survival.

Results: The expression of AP-2alpha in carcinomas was usually weak and cytoplasmic, similar to normal prostatic epithelium adjacent to tumors. In 6% of the tumors, the expression was strong, and in 15% no staining signal was detected. Nuclear expression was detected in 22% of cases. Low fraction of AP-2-expressing cells was related to high mitotic index, Ki67 labeling and high expression of p21 (waf1/cip1). Nuclear expression of AP-2 was related to high Gleason score, advanced T category, DNA aneuploidy and high S-phase fraction. Nuclear expression was an indicator of unfavorable disease outcome, but in multivariate analysis, expression of AP-2 had no prognostic value.

Conclusions: Cytoplasmic expression of AP-2alpha is reduced in poorly differentiated prostate carcinomas. The rare nuclear expression occurs in a small proportion of tumors which are aneuploid, have a high T category and high Gleason score. The expression of AP-2 seems to have no prognostic value in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Division
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / biosynthesis*
  • DNA-Binding Proteins / biosynthesis*
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology*

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • DNA-Binding Proteins
  • activator protein-2 binding element