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

Smiraglia, Dominic J.
Bshara, Wiam
Andrews, Christopher
Schwaller, Juerg
South, Stacey
Higgs, Donald
Lele, Shashikant
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Published in Cancer Epidemiology, Biomarkers & Prevention. 2008, vol. 17, no. 3, p. 571-577
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 AdultAgedAged, 80 and overAnalysis of VarianceAntigens, Surface/*metabolismCell Line, TumorDown-RegulationEndometrial Neoplasms/*metabolismFemaleGlutamate Carboxypeptidase II/*metabolismHumansImmunoenzyme TechniquesMiddle AgedPrognosisProportional Hazards ModelsReverse Transcriptase Polymerase Chain ReactionTumor Markers, Biological/metabolism
PMID: 18349274
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Other version: http://cebp.aacrjournals.org/content/17/3/571.full.pdf
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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 https://archive-ouverte.unige.ch/unige:19071

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Deposited on : 2012-03-27

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