Scientific article
English

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

Published inCancer epidemiology, biomarkers & prevention, vol. 17, no. 3, p. 571-577
Publication date2008
Abstract

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.

Keywords
  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antigens, Surface/*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
  • Tumor Markers, Biological/metabolism
Citation (ISO format)
MHAWECH-FAUCEGLIA, Paulette et al. Prostate-specific membrane antigen expression is a potential prognostic marker in endometrial adenocarcinoma. In: Cancer epidemiology, biomarkers & prevention, 2008, vol. 17, n° 3, p. 571–577. doi: 10.1158/1055-9965.EPI-07-0511
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ISSN of the journal1055-9965
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