Tissue microarray analysis reveals prognostic significance of syndecan-1 expression in prostate cancer

Prostate. 2003 Apr 1;55(1):20-9. doi: 10.1002/pros.10209.

Abstract

Background: Tissue microarrays (TMA) have recently emerged as powerful tools to rapidly analyze the clinical significance of new molecular markers in human tumors. Here, we have tested several molecular markers on a prostate TMA containing 637 different specimens.

Methods: The specimens were from 551 patients with prostate cancer and long-term follow-up information on progression (median 5.3 years), tumor-specific and overall survival (median 5.9 years). Eighty-six specimens from benign prostatic hyperplasia were included as controls. Expression of Ki67, Bcl-2, p53, CD-10 (neutral endopeptidase), and syndecan-1 (CD-138) was analyzed by immunohistochemistry.

Results: Gleason grade and Ki67 Labeling Index (LI) were independent predictors of early recurrence and poor survival. Bcl-2 predicted early recurrence, whereas p53 was associated with poor survival. Syndecan-1 overexpression also predicted early recurrence and was significantly associated with tumor specific survival, high Gleason grade, Ki67 LI, and Bcl-2 overexpression. Neoadjuvant hormonal therapy was associated with overexpression of Bcl-2 and inhibition of Ki67 LI and CD-10, but did not affect the expression of the remaining markers.

Conclusions: The results of this TMA study confirm a dominant prognostic significance of Gleason grading and Ki67 LI in prostate cancer, as compared to a less pronounced role of Bcl-2, and p53. We identified syndecan-1 as a new prognostic factor and provide evidence for an androgen-dependent regulation of CD-10 expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Down-Regulation
  • Genes, bcl-2 / physiology
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Neprilysin / metabolism
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Protein Array Analysis / methods
  • Proteoglycans / biosynthesis*
  • Retrospective Studies
  • Syndecan-1
  • Syndecans
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Ki-67 Antigen
  • Membrane Glycoproteins
  • Proteoglycans
  • SDC1 protein, human
  • Syndecan-1
  • Syndecans
  • Tumor Suppressor Protein p53
  • Neprilysin