Prostate-specific membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma

Cancer Epidemiol Biomarkers Prev. 2008 Mar;17(3):571-7. doi: 10.1158/1055-9965.EPI-07-0511.


The aim of this study was to determine the role of prostate-specific membrane antigen (PSMA) as a prognostic marker in endometrial adenocarcinoma (EAC) and to explore whether its down-regulation could be due to epigenetic mechanism. First, we examined the expression and the prognostic value of PSMA by semiquantitative reverse transcription-PCR and immunohistochemistry in EAC tissue samples. Second, to explore the role of CpG methylation in down-regulation PSMA in EAC, we evaluated PSMA CpG island methylation using methylation-specific PCR in cells lines and in a subset of patients' samples. Furthermore, association of the status of tumor methylation to the clinical and histologic variables was also evaluated. Higher PSMA mRNA levels were associated with stage I (P = 0.046) and PSMA protein intensity by immunohistochemistry (P = 0.032). In multivariate analysis, loss of PSMA expression was associated with a worse disease-free survival (P = 0.02). PSMA was methylated in prostate cell lines (DU145 and PC3) and endometrial cell lines. In addition, PSMA was methylated in 5 of 18 samples (all 5 had low PSMA mRNA value). There was a significant association between PSMA methylation and loss of protein expression by immunohistochemistry and PSMA-RNA level with P value of 0.036 and 0.011, respectively. In addition, there was an association between PSMA methylation and tumor size (P = 0.025). In summary, (a) PSMA is underexpressed in advanced stage EAC, (b) loss of PSMA expression can be considered as a prognostic marker in patients with EAC, and (c) loss of PSMA expression in a subset of EAC cases could be due to epigenetic silencing.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antigens, Surface / metabolism*
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Down-Regulation
  • Endometrial Neoplasms / metabolism*
  • Female
  • Glutamate Carboxypeptidase II / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Middle Aged
  • Prognosis
  • Proportional Hazards Models
  • Reverse Transcriptase Polymerase Chain Reaction


  • Antigens, Surface
  • Biomarkers, Tumor
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II