Prostate Stem Cell Antigen is a genetic indicator for development of gestational trophoblastic neoplasia

Abstract

Objectives: Hydatidiform mole (HM) is the most common type of gestational trophoblastic diseases (GTD). HM can be considered as abnormal conceptuses capable of developing persistent disease or gestational trophoblastic neoplasia (GTN) requiring chemotherapy in a portion of cases. Few biological parameters, except serial HCG assays, have been found useful in predicting the progress of HM to GTN. Methods: Differential expression analysis was performed to identifiy genes that may play a role in development of GTN. HM that spontaneously regressed and that subsequently developed metastatic GTN was compared using the Stanford Human cDNA chip (41, 421 cDNA features). Verification by quantitative RNA analysis by Real-time PCR and immunohistochemical analysis was performed in 23 complete HM genotyped by microsatellite analysis and chromosome in situ hybridization analysis. Results: Approximately 70 differentially expressed genes with ratio more than 3 were identified. They were involved in cell growth, substance transport, anti-coagulation, higher invasive potential and lower metabolism. Four genes were chosen for quantitative RNA analysis, including prostate stem cell antigen (PSCA, p=0.037), aquaporin 3 (AQP3, p=0.455), transforming growth factor beta 2 (TGFB2, p=0.164) and retinol binding protein 1 (RBP1, p=0.128). Up-regulation of PSCA in GTN was further confirmed with immunohistochemical analysis (p=0.0273). Conclusion: Over-expression of PSCA was associated with development of GTN. Stem cells may share cellular characteristics of cancer cells such as capacity of self renewal. Further study on PSCA in GTN may provide a better understanding of its pathogenesis. The potential application of PSCA in management of patient with HM may be explored.