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

The aim of this study was to determine the role of prostate-specific membrane antigen (PSMA) as a prognostic marker in endometrial adenocarcinoma (EAC) andto explore whether its down-regulation couldbe due to epigenetic mechanism. First, we examinedthe expression and the prognostic value of PSMA by semiquantitative reverse transcription-PCR andimmunohistochemistry in EAC tissue samples. Second, to explore the role of CpG methylation in down-regulation PSMA in EAC, we evaluated PSMA CpG islandme thylation using methylation-specific PCR in cells lines andin a subset of patients' samples. Furthermore, association of the status of tumor methylation to the clinical andhistologic 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 associatedwith a worse disease-free survival (P = 0.02). PSMA was methylatedin prostate cell lines (DU145 and PC3) and endometrial cell lines. In addition, PSMA was methylatedin 5 of 18 samples (all 5 hadlow PSMA mRNA value). There was a significant association between PSMA methylation andloss of protein expression by immunohistochemistry and PS MA-RNA level with P value of 0.036 and 0.011, respectively. In addition, there was an association between PSMA methylation andtumor 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 couldbe due to epigenetic silencing.