Monophasic and biphasic synovial sarcomas abundantly express cancer/testis antigen NY-ESO-1 but not MAGE-A1 or CT7.
Synovial sarcomas are high-grade malignant mesenchymal tumors with biphasic (BSS) and monophasic (MSS) variants that carry a pathognomonic cytogenetic alteration, t(X;18), involving the SYT gene on chromosome 18 and one of several SSX genes on chromosome X, usually SSX1 or SSX2. Cancer/testis (CT) antigens are expressed in a variety of malignant neoplasms but, in normal tissues, are restricted to male germ cells. Previous analysis revealed a high incidence and homogeneous expression of MAGE CT antigen in synovial sarcomas. The present study was performed to analyze the expression of 3 CT antigens, NY-ESO-1, MAGE-A1 and CT7, by immunohistochemistry with 3 monoclonal antibodies (MAbs), ES121 (anti-NY-ESO-1), MA454 (anti-MAGE-A1) and CT7-33 (anti-CT7), in 25 synovial sarcomas (12 MSS, 13 BSS) typed for the t(X;18)-derived fusion transcript by RT-PCR (19 SYT-SSX1, 6 SYT-SSX2). NY-ESO-1 immunoreactivity was found in 20/25 (80%) cases, and antigen expression was homogeneous in 14/20 NY-ESO-1-positive cases. Both morphologic variants and both translocation types were NY-ESO-1-positive, whereas 5 SYT-SSX1 tumors (1 MSS, 4 BSS) were NY-ESO-1-negative. MAb MA454 was immunoreactive with 4/25 cases (2 MSS, 2 BSS; 3 SYT-SSX1, 1 SYT-SSX2), and MAb CT7-33 was immunoreactive with only 2/25 cases (both BSS, SYT-SSX1). Expression of MAGE-A1 and CT7 was heterogeneous in all positive cases. Our study shows that NY-ESO-1 is highly expressed in a homogeneous pattern in synovial sarcomas of both morphologic variants and both translocation types, making these tumors an attractive target for NY-ESO-1 antigen-based immunotherapy.
Jungbluth
A A
AA
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. jungblua@mskcc.org
Antonescu
C R
CR
Busam
K J
KJ
Iversen
K
K
Kolb
D
D
Coplan
K
K
Chen
Y T
YT
Stockert
E
E
Ladanyi
M
M
Old
L J
LJ
D000951:Antigens, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000032:analysis*; D011506:Proteins / Q000032:analysis*; D013584:Sarcoma, Synovial / Q000276:immunology*
D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; C110905:MAGEC1 protein, human; D058950:Melanoma-Specific Antigens; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D011506:Proteins