Oncotarget

Research Papers:

Comprehensive adipocytic and neurogenic tissue microarray analysis of NY-ESO-1 expression - a promising immunotherapy target in malignant peripheral nerve sheath tumor and liposarcoma

Elizabeth Shurell, Maria E. Vergara-Lluri, Yunfeng Li, Joseph G. Crompton, Arun Singh, Nicholas Bernthal, Hong Wu, Fritz C. Eilber _ and Sarah M. Dry

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Oncotarget. 2016; 7:72860-72867. https://doi.org/10.18632/oncotarget.12096

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Abstract

Elizabeth Shurell1,*, Maria E. Vergara-Lluri2,*, Yunfeng Li3, Joseph G. Crompton1, Arun Singh4, Nicholas Bernthal5, Hong Wu3, Fritz C. Eilber1, Sarah M. Dry2

1Division of Surgical Oncology, University of California, Los Angeles, CA 90095, USA

2Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095, USA

3Department of Molecular and Medical Pharmacology, University of California, Los Angeles, CA 90095, USA

4Department of Hematology/Oncology, University of California, Los Angeles, CA 90095, USA

5Department of Orthopaedic Surgery, University of California, Los Angeles, CA 90095, USA

*Co-first author

Correspondence to:

Fritz C. Eilber, email: [email protected]

Keywords: NY-ESO-1, sarcoma, MPNST, liposarcoma, immunotherapy

Received: July 28, 2016     Accepted: September 09, 2016     Published: September 17, 2016

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.


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