Overexpression of prostate stem cell antigen is associated with gestational trophoblastic neoplasia.
OBJECTIVE
Hydatidiform mole (HM) is the most common type of gestational trophoblastic disease. A proportion of patients with HM develop gestational trophoblastic neoplasia (GTN) requiring chemotherapy. The aim was to identify differentially expressed genes that are associated with development of GTN.


RESULTS
Using cDNA microarray, differential expression of prostate stem cell antigen (PSCA) was identified in HMs that developed GTN compared with those that spontaneously regressed. Significant overexpression of PSCA RNA (P = 0.037) and protein (P < 0.05) in aggressive HM was verified by real-time polymerase chain reaction (PCR) and immunohistochemical analysis in 10 first-trimester placentas, 36 HM that subsequently regressed and 11 HM that developed GTN. A high level of PSCA expression was also found in three choriocarcinomas and three placental site trophoblastic tumours. A positive correlation was observed between PSCA expression and proliferation and apoptotic indices as assessed by Ki67 (P = 0.01), mcm7 (P = 0.001) and M30 (P = 0.016), as well as p53 (P < 0.01), p21(WAF1/CIP1) (P < 0.01) and mdm2 (P = 0.002) expression.


CONCLUSIONS
Overexpression of PSCA is associated with development of GTN in HM. PSCA probably plays a role in the regulation of cell growth through p53-related signaling pathways.
Feng
H C
HC
Department of Anatomy, The University of Hong Kong, Queen Mary Hospital, Hong Kong.
Tsao
S W
SW
Ngan
H Y S
HY
Xue
W C
WC
Kwan
H-S
HS
Siu
M K Y
MK
Liao
X-Y
XY
Wong
E
E
Cheung
A N Y
AN
D000293:Adolescent; D000328:Adult; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor / Q000378:metabolism; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D015972:Gene Expression Regulation, Neoplastic; D031901:Gestational Trophoblastic Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011247:Pregnancy; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human; D016159:Tumor Suppressor Protein p53