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) 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.
Mhawech-Fauceglia
Paulette
P
Department of Pathology, Roswell Park Cancer Institute, Elm and Carlton Street, Buffalo, NY 14263, USA. pmhawech1@yahoo.com
Smiraglia
Dominic J
DJ
Bshara
Wiam
W
Andrews
Christopher
C
Schwaller
Juerg
J
South
Stacey
S
Higgs
Donald
D
Lele
Shashikant
S
Herrmann
Francois
F
Odunsi
Kunle
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000954:Antigens, Surface / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000378:metabolism*; D005260:Female; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000954:Antigens, Surface; D014408:Biomarkers, Tumor; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II