NY-ESO-1, a Cancer/Testis Antigen, Is Differentially Expressed in Myxoid/Round Cell Liposarcomas Compared to Other Liposarcoma Subtypes and Myxomatous Neoplasms
Jessica Hemminger, Thomas Scharschmidt, Joel Mayerson, William Kraybill, O Hans Iwenofu. The Ohio State University Medical Center, Columbus, OH
Background: NY-ESO-1 is a highly immunogenic cancer/testis antigen (CTA) expressed in testicular germ cells and in various cancers where it can induce cellular and humoral immunity. Immunotherapy targeting this antigen has shown promise in clinical trials involving NY-ESO-1 expressing tumors, including synovial sarcomas, melanomas and solid organ tumors. Liposarcomas (LPS) are common soft tissue sarcomas, and surgery with or without chemoradiation therapy remains the main stay of treatment. Gene expression studies have shown upregulation of CTAs in LPS, particularly the myxoid/round cell (MRCL) subtype. Herein, we evaluated the expression of NY-ESO-1 antigen among a variety of lipomatous and related myxomatous neoplasms by immunohistochemistry (IHC) using a monoclonal antibody to NY-ESO-1.
Design: Formalin-fixed paraffin-embedded (FFPE) blocks were obtained for lipomas (n=19; 3 with myxoid change) and the following LPS subtypes (n=44): MRCL (n=18); well-differentiated (n=10; 2 with myxoid change); dedifferentiated (n=10); and pleomorphic (n=6). FFPE blocks were also retrieved for the following myxomatous neoplasms (n=15): low grade fibromyxoid sarcoma (LGFS, n=5); myxofibrosarcoma (MFS, n=5); and myxoma (n=5). Utilizing standard IHC staining protocols, full sections were stained with NY-ESO-1 (clone E978; Santa Cruz Biotechnology). Staining was assessed for intensity (1-3+), percentage of tumor positivity and location.
Results: 16/18 (89%) MRCL expressed NY-ESO-1. The majority demonstrated uniform staining (>75% positive cells) of moderate to strong intensity (2-3+), while two cases showed a more heterogenous pattern: 3+ intensity in 60% of cells and 1+ intensity in 20% of cells. 3/6 (50%) pleomorphic LPS 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 (10%) case of dedifferentiated LPS showed strong, diffuse staining (3+ intensity in 75% of cells). In all positive instances, both nuclear and cytoplasmic staining was present. There was no immunoreactivity seen in lipomas, well-differentiated LPS, LGFS, MFS or myxomas.
Conclusions: Our data indicate that NY-ESO-1 is expressed with high frequency in MRCL and can be of diagnostic utility within the differential diagnosis, which includes other myxoid neoplasms, such as well-differentiated LPS with myxoid change, soft tissue myxomas and MFS. Furthermore, the high level of NY-ESO-1 expression in MRCL enables the potential use of targeted immunotherapy in the treatment of this malignancy.
Category: Bone & Soft Tissue
Monday, March 19, 2012 1:00 PM
Poster Session II # 10, Monday Afternoon