title: Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma.
abstract: BACKGROUND
  Immunotherapy targeting cancer-testis antigen NY-ESO-1 shows promise for tumors with poor response to chemoradiation. Malignant peripheral nerve sheath tumors (MPNSTs) and liposarcomas (LPS) are chemoresistant and have few effective treatment options. Materials Methods: Using a comprehensive tissue microarray (TMA) of both benign and malignant tumors in primary, recurrent, and metastatic samples, we examined NY-ESO-1 expression in peripheral nerve sheath tumor (PNST) and adipocytic tumors. The PNST TMA included 42 MPNSTs (spontaneous n = 26, NF1-associated n = 16), 35 neurofibromas (spontaneous n = 22, NF-1 associated n = 13), 11 schwannomas, and 18 normal nerves. The LPS TMA included 48 well-differentiated/dedifferentiated (WD/DD) LPS, 13 myxoid/round cell LPS, 3 pleomorphic LPS, 8 lipomas, 1 myelolipoma, and 3 normal adipocytic tissue samples. Stained in triplicate, NY-ESO-1 intensity and density were scored.
  
  
  RESULTS
  NY-ESO-1 expression was exclusive to malignant tumors. 100% of myxoid/round cell LPS demonstrated NY-ESO-1 expression, while only 6% of WD/DD LPS showed protein expression, one of which was WD LPS. Of MPNST, 4/26 (15%) spontaneous and 2/16 (12%) NF1-associated MPNSTs demonstrated NY-ESO-1 expression. Strong NY-ESO-1 expression was observed in myxoid/round cell and dedifferentiated LPS, and MPNST in primary, neoadjuvant, and metastatic settings.
  
  
  CONCLUSIONS
  We found higher prevalence of NY-ESO-1 expression in MPNSTs than previously reported, highlighting a subset of MPNST patients who may benefit from immunotherapy. This study expands our understanding of NY-ESO-1 in WD/DD LPS and is the first demonstration of staining in a WD LPS and metastatic/recurrent myxoid/round cell LPS. These results suggest immunotherapy targeting NY-ESO-1 may benefit patients with aggressive tumors resistant to conventional therapy.
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Shurell
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Maria E
authors.initials: ME
authors.lastname: Vergara-Lluri
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Crompton
authors.affiliation: Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Arun
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bernthal
authors.affiliation: Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.affiliation: Division of Surgical Oncology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Fritz C
authors.initials: FC
authors.lastname: Eilber
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Dry
mesh_terms: D050156:Adipogenesis / Q000235:genetics; D000273:Adipose Tissue / Q000378:metabolism*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy; D008080:Liposarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009417:Nerve Tissue / Q000378:metabolism*; D055495:Neurogenesis; D046888:Tissue Array Analysis / Q000379:methods
chemical_list: D000951:Antigens, Neoplasm; D015415:Biomarkers; C104948:CTAG1B protein, human; D008565:Membrane Proteins
keywords: MPNST; NY-ESO-1; immunotherapy; liposarcoma; sarcoma