title: The cancer-testis antigen NY-ESO-1 is highly expressed in myxoid and round cell subset of liposarcomas.
abstract: Liposarcomas are a heterogenous group of fat-derived sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. NY-ESO-1 is a cancer-testis antigen expressed in various cancers where it can induce both cellular and humoral immunity. Immunotherapy has shown promise in clinical trials involving NY-ESO-1-expressing tumors. Gene expression studies have shown upregulation of the gene for NY-ESO-1, CTAG1B, in myxoid and round cell liposarcomas. Herein, we evaluated the expression of NY-ESO-1 among liposarcoma subtypes by quantitative real-time PCR, western blot analysis, and immunohistochemistry. Frozen tissue for quantitative real-time PCR and western blot analysis was obtained for the following liposarcoma subtypes (n=15): myxoid and round cell (n=8); well-differentiated (n=4), and dedifferentiated (n=3). Formalin-fixed paraffin-embedded blocks were obtained for the following liposarcoma subtypes (n=44): myxoid and round cell (n=18); well-differentiated (n=10); dedifferentiated (n=10); and pleomorphic (n=6). Full sections were stained with monoclonal antibody NY-ESO-1, and staining was assessed for intensity (1-3+), percentage of tumor positivity, and location. In all, 7/8 (88%) and 16/18 (89%) myxoid and round cell expressed CTAG1B and NY-ESO-1 by quantitative real-time PCR and immunohistochemistry, respectively. Western blot correlated with mRNA expression levels. By immunohistochemistry, 94% (15/16) of positive cases stained homogenously with 2-3+ intensity. Also, 3/6 (50%) pleomorphic liposarcomas demonstrated a range of staining: 1+ intensity in 50% of cells; 2+ intensity in 5% of cells; and 3+ intensity in 90% of cells. One case of dedifferentiated liposarcoma showed strong, diffuse staining (3+ intensity in 75% of cells). Our study shows that both CTAG1B mRNA and protein are overexpressed with high frequency in myxoid and round cell liposarcoma, enabling the potential use of targeted immunotherapy in the treatment of this malignancy.
authors.affiliation: Department of Pathology and Laboratory Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Hemminger
authors.forename: Amanda
authors.initials: A
authors.lastname: Ewart Toland
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scharschmidt
authors.forename: Joel L
authors.initials: JL
authors.lastname: Mayerson
authors.forename: William G
authors.initials: WG
authors.lastname: Kraybill
authors.forename: Denis C
authors.initials: DC
authors.lastname: Guttridge
authors.forename: O Hans
authors.initials: OH
authors.lastname: Iwenofu
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012189:Retrospective Studies; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D013737:Testis / Q000378:metabolism* / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D008565:Membrane Proteins