Methylation of multiple genes in prostate cancer and the relationship with clinicopathological features of disease

Oncol Rep. 2004 Sep;12(3):631-7.


Promoter methylation plays an important role in the inactivation of tumor suppressor genes during tumorigenesis. We examined the methylation status of glutathione s-transferase Pi1 (GSTP1), retinoic acid receptor beta (RARB), CD44, E-cadherin (ECAD), RAS association domain family protein 1A (RASSF1A) and endothelin B receptor (EDNRB) genes in 81 prostate cancer and 42 benign prostatic hyperpasia specimens. Genomic DNA was isolated from archived formaldehyde-fixed and paraffin-embedded tissue blocks. Methylation-specific PCR (MSP) was carried out after bisulfite treatment of genomic DNA. Methylation frequencies in prostate cancer and benign prostatic hyperplasia were 72% and 5% for GSTP1, 40% and 0% for RARB, 72% and 38% for CD44, 61% and 14% for ECAD, 49% and 19% for RASSF1A and 72% and 62% for EDNRB, respectively. Methylation of GSTP1, RARB, CD44, ECAD and RASSF1A, but not of EDNRB was detected at a statistically higher frequency in prostate cancer than in the benign prostatic hypertrophy specimens. Methylation of RARB occurred more frequently in early onset (age <55 years) as compared to late onset disease (age >70 years) (odds ratio, 8.6; 95% CI, 1.4-51.4; P=0.02). Methylation of RARB also occurred more frequently in stage III as compared to stage II disease (odds ratio, 3.2; 95% CI, 1.1-8.8; P=0.03). A methylation index (MI) was calculated as the total number of genes methylated, excluding EDNRB. A trend toward higher MI was noted in stage III as compared to stage II disease, and in Gleason score 7 as compared to Gleason score 6 tumors. Our results suggest that the methylation of selected genes in prostate cancers correlates with clinicopathological features of poor prognosis.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Cadherins / genetics
  • DNA / metabolism
  • DNA Methylation*
  • Glutathione S-Transferase pi
  • Glutathione Transferase / genetics
  • Humans
  • Hyaluronan Receptors / genetics
  • Isoenzymes / genetics
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymerase Chain Reaction
  • Prognosis
  • Promoter Regions, Genetic
  • Prostatic Hyperplasia / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptor, Endothelin B / genetics
  • Receptors, Retinoic Acid / genetics
  • Tumor Suppressor Proteins / genetics


  • Cadherins
  • Hyaluronan Receptors
  • Isoenzymes
  • RASSF1 protein, human
  • Receptor, Endothelin B
  • Receptors, Retinoic Acid
  • Tumor Suppressor Proteins
  • retinoic acid receptor beta
  • DNA
  • GSTP1 protein, human
  • Glutathione S-Transferase pi
  • Glutathione Transferase