Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia

Prostate Cancer Prostatic Dis. 2004;7(4):321-6. doi: 10.1038/sj.pcan.4500749.

Abstract

Introduction: Benign prostatic hyperplasia (BPH) is a slowly progressive abnormal glandular enlargement with heterogeneous morphology. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in this common and significantly morbid disease.

Methods: Prostatic tissue from 20 patients with BPH and no prior or subsequent prostatic carcinoma was obtained by transurethral prostatectomy (TURP) at the University of California Davis. Apoptotic regulatory proteins: BCL2, BAX and p27 were analyzed by immunohistochemistry and evaluated for expression in four distinct histologic patterns: hyperplastic epithelium, nodules, dilated glands and atrophic/inflammatory glands.

Results: Particularly striking was the decreased expression of BAX and an abnormal BCL2 : BAX ratio within all nodules relative to expression in other epithelial patterns. p27 expression was decreased in 35% of the hyperplastic epithelial areas and 10% of the nodules.

Discussion: Overall, abnormal expression of BCL2, BAX and/or p27 was identified in the hyperplastic epithelium of 19 (90%) of specimens and all 12 (100%) of the hyperplastic nodules. The high frequency of abnormalities in apoptosis regulatory genes, suggests that alteration of apoptotic pathways is important for the development of this condition.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • Cell Cycle Proteins / metabolism*
  • Cell Cycle*
  • Cyclin-Dependent Kinase Inhibitor p27
  • Down-Regulation
  • Enzyme Inhibitors / metabolism
  • Epithelial Cells / metabolism
  • Genes, Tumor Suppressor
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Prostatic Hyperplasia / metabolism*
  • Prostatic Hyperplasia / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Stromal Cells / metabolism
  • Tumor Suppressor Proteins / metabolism*
  • bcl-2-Associated X Protein

Substances

  • BAX protein, human
  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Proteins
  • bcl-2-Associated X Protein
  • Cyclin-Dependent Kinase Inhibitor p27