Expression of cancer-testis antigens MAGEA1, MAGEA3, ACRBP, PRAME, SSX2, and CTAG2 in myxoid and round cell liposarcoma.
Myxoid and round-cell liposarcoma is a frequently encountered liposarcoma subtype. The mainstay of treatment remains surgical excision with or without chemoradiation. However, treatment options are limited in the setting of metastatic disease. Cancer-testis antigens are immunogenic antigens with the expression largely restricted to testicular germ cells and various malignancies, making them attractive targets for cancer immunotherapy. Gene expression studies have reported the expression of various cancer-testis antigens in liposarcoma, with mRNA expression of CTAG1B, CTAG2, MAGEA9, and PRAME described specifically in myxoid and round-cell liposarcoma. Herein, we further explore the expression of the cancer-testis antigens MAGEA1, ACRBP, PRAME, and SSX2 in myxoid and round-cell liposarcoma by immunohistochemistry in addition to determining mRNA levels of CTAG2 (LAGE-1), PRAME, and MAGEA3 by quantitative real-time PCR. Samples in formalin-fixed paraffin-embedded blocks (n=37) and frozen tissue (n=8) were obtained for immunohistochemistry and quantitative real-time PCR, respectively. Full sections were stained with antibodies to MAGEA1, ACRBP, PRAME, and SSX2 and staining was assessed for intensity (1-2+) and percent tumor positivity. The gene expression levels of CTAG2, PRAME, and MAGEA3 were measured by quantitative real-time PCR. In total, 37/37 (100%) of the samples showed predominantly strong, homogenous immunoreactivity for PRAME. There was a variable, focal expression of MAGEA1 (11%) and SSX2 (16%) and no expression of ACRBP. Quantitative real-time PCR demonstrated PRAME and CTAG2 transcripts in all eight samples: six tumors with high mRNA levels; two tumors with low mRNA levels. The gene expression of MAGEA3 was not detected in the majority of cases. In conclusion, myxoid and round-cell liposarcomas consistently express PRAME by immunohistochemistry as well as CTAG2 and PRAME by qualitative real-time PCR. This supports the use of cancer-testis antigen-targeted immunotherapy in the treatment of this malignancy.
Department of Pathology and Laboratory Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
Jessica A
JA
Hemminger
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Amanda Ewart
0000000202711792
AE
Toland
Department of Orthopedics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Thomas J
TJ
Scharschmidt
Department of Orthopedics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Joel L
JL
Mayerson
Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
Denis C
DC
Guttridge
Department of Pathology and Laboratory Medicine, Wexner Medical Center at The Ohio State University, Columbus, OH, USA.
O Hans
OH
Iwenofu
D000951:Antigens, Neoplasm / Q000235:genetics* / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics; D014408:Biomarkers, Tumor; D002352:Carrier Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D018208:Liposarcoma, Myxoid / Q000235:genetics* / Q000378:metabolism*; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012097:Repressor Proteins / Q000378:metabolism
C485651:ACRBP protein, human; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D014408:Biomarkers, Tumor; C510162:CTAG2 protein, human; D002352:Carrier Proteins; C072011:MAGEA1 protein, human; C072013:MAGEA3 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; C404944:PRAME protein, human; D012333:RNA, Messenger; D012097:Repressor Proteins; C093962:synovial sarcoma X breakpoint proteins