Chromosome X-encoded cancer/testis antigens show distinctive expression patterns in developing gonads and in testicular seminoma.
BACKGROUND
Cancer/testis (CT) antigens are cancer antigens normally expressed in adult testicular germ cells. The expression of chromosome X-encoded CT antigens (CT-X antigens) in human fetal gonads and in testicular seminomas was examined.


METHODS
The expression of 10 CT-X antigens (MAGEA, NY-ESO-1, GAGE, CT7/MAGEC1, CT10/MAGEC2, CT45, SAGE1, SSX2, NXF2 and SPANX) was studied immunohistochemically.


RESULTS
In adult human testis, SPANX is expressed in late spermatids and spermatozoa, whereas all other CT-X antigens are predominantly expressed in spermatogonia or primary spermatocytes. All CT-X antigens except SPANX are expressed in human fetal germ cells. CT-X-positive germ cells appear as early as 13 weeks after gestation, increase with age and reach a plateau at around 22 weeks. In the fetal ovary, CT-X-positive oogonia are most abundant at around 24 weeks and sharply decrease subsequently. CT-X antigens are almost exclusively expressed in OCT3/4-negative gonocytes and their expression appears to coincide with the loss of pluripotency. Spermatocytic seminoma, a neoplasm derived from adult pre-meiotic germ cells, showed uniform expression of all CT-X antigens except SPANX. In contrast, most seminomas (>80%) express CT7, CT45, GAGE and CT10 but express MAGEA, NXF2 and NY-ESO-1 at lower frequency, and very rarely express SSX2 and SAGE1.


CONCLUSIONS
Most CT-X antigens are expressed in human fetal germ cells after they have lost stem cell characteristics, with predominant expression in pre-meiotic germ cells. Spermatocytic seminomas showed expression of all CT-X antigens except SPANX, whereas classical seminomas only express some CT-X antigens, reflecting their different origins from adult versus fetal germ cells.
Weill Cornell Medical College, 1300 York Avenue, New York, NY 10021, USA. ytchen@med.cornell.edu
Yao-Tseng
YT
Chen
Rita
R
Chiu
Peishan
P
Lee
Debra
D
Beneck
Boquan
B
Jin
Lloyd J
LJ
Old
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D041321:Chromosomes, Human, X; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D018239:Seminoma / Q000235:genetics / Q000378:metabolism*; D013094:Spermatozoa / Q000378:metabolism; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000166:cytology* / Q000196:embryology / Q000378:metabolism
D000951:Antigens, Neoplasm; C502804:CT45A1 protein, human; C473332:CT7 antigen, human; C104948:CTAG1B protein, human; C405429:MAGEC2 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C412325:SAGE1 protein, human; C414403:SPANXA1 protein, human; C542434:cancer testis antigen NXF2, human; C093962:synovial sarcoma X breakpoint proteins