Transcriptional repression of RUNX2 is associated with aggressive clinicopathological outcomes, whereas nuclear location of the protein is related to metastasis in prostate cancer

Prostate Cancer Prostatic Dis. 2012 Dec;15(4):369-73. doi: 10.1038/pcan.2012.31. Epub 2012 Aug 14.

Abstract

Background: Runt-related transcription factor 2 (RUNX2) is a transcription factor that is closely related to bone formation, and prostate cancer (CaP) is the most common cancer to metastasize to bone. The present study investigated the expression levels of RUNX2 in human prostate tissue, and the correlation between RUNX2 levels and the clinicopathological characteristics of CaP.

Methods: A case-control study was conducted including 114 cases of newly diagnosed CaP and 114 age-matched BPH patients as controls. RUNX2 expression was estimated using real-time PCR and immunohistochemical staining.

Results: The mRNA expression of RUNX2 did not differ between CaP tissues and non-cancer BPH controls (P=0.825). However, RUNX2 expression was significantly decreased in patients with elevated PSA levels (≥20 ng ml(-1)), a Gleason score ≥8 and metastatic disease compared to those with low PSA, low Gleason score and non-metastatic disease (P=0.023, 0.005 and 0.014, respectively). Immunohistochemical analysis showed that 65.2% of the patients with positive RUNX2 nuclear staining had metastatic disease, which was present in only 25.9% of those with negative staining (P=0.010).

Conclusions: RUNX2 mRNA expression was negatively correlated with CaP aggressiveness. Moreover, the nuclear location of RUNX2 may be a prognostic marker of metastasis in CaP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms* / genetics
  • Bone Neoplasms* / pathology
  • Bone Neoplasms* / secondary
  • Cell Nucleolus / metabolism
  • Cell Nucleolus / ultrastructure
  • Core Binding Factor Alpha 1 Subunit* / genetics
  • Core Binding Factor Alpha 1 Subunit* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Transcription, Genetic*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • RUNX2 protein, human