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Prostate-Specific Membrane Antigen Expression Is a Potential Prognostic Marker in Endometrial Adenocarcinoma

Departments of ¹ Pathology and Laboratory Medicine, ² Cancer Genetics, and ³ Gynecology-Oncologic Surgery, Roswell Park Cancer Institute; ⁴ Department of Biostatistics, University of Buffalo, Buffalo, New York; ⁵ Department of Research, BaselUniversity Hospital, Basel, Switzerland; and ⁶ Department of Rehabilitation and Geriatrics, Geneva University Hospital, Geneva, Switzerland

Requests for reprints: Paulette Mhawech-Fauceglia, Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Street, Buffalo, NY 14263. Phone: 716-845-3204; Fax: 716-845-3427. E-mail: pmhawech1{at}yahoo.com and Paulette.mhawech-fauceglia{at}roswellpark.org

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. (Cancer Epidemiol Biomarkers Prev 2008;17(3):571–7)