Oncotarget

Research Papers:

MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy

Simon Laban _, Gregor Giebel, Niklas Klümper, Andreas Schröck, Johannes Doescher, Giulio Spagnoli, Julia Thierauf, Marie-Nicole Theodoraki, Romain Remark, Sacha Gnjatic, Rosemarie Krupar, Andrew G. Sikora, Geert Litjens, Niels Grabe, Glen Kristiansen, Friedrich Bootz, Patrick J. Schuler, Cornelia Brunner, Johannes Brägelmann, Thomas K. Hoffmann and Sven Perner

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Oncotarget. 2017; 8:14719-14735. https://doi.org/10.18632/oncotarget.14830

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Abstract

Simon Laban1, Gregor Giebel1, Niklas Klümper2, Andreas Schröck3, Johannes Doescher1, Giulio Spagnoli4, Julia Thierauf1, Marie-Nicole Theodoraki1, Romain Remark5, Sacha Gnjatic5, Rosemarie Krupar2,6, Andrew G. Sikora6, Geert Litjens7, Niels Grabe7, Glen Kristiansen8, Friedrich Bootz3, Patrick J. Schuler1, Cornelia Brunner1, Johannes Brägelmann9, Thomas K. Hoffmann1,*, Sven Perner2,*

1Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany

2Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Germany

3Department of Otorhinolaryngology, University Hospital Bonn, Bonn, Germany

4Department of Biomedicine, University Hospital Basel, Basel, Switzerland

5Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York City, NY, USA

6Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA

7Hamamatsu Tissue Imaging and Analysis Center, BIOQUANT, University of Heidelberg, Heidelberg, Germany

8Institute of Pathology, University Hospital Bonn, Bonn, Germany

9Department of Oncology, University Hospital Bonn, Bonn, Germany

*These authors contributed equally to this manuscript and share senior authorship

Correspondence to:

Simon Laban, email: [email protected]

Keywords: cancer-testis antigens, MAGE, melanoma-associated antigen, head and neck squamous cell carcinoma, HNSCC

Received: October 29, 2016     Accepted: January 16, 2017     Published: January 27, 2017

ABSTRACT

Melanoma associated antigens (MAGE) are potential targets for immunotherapy and have been associated with poor overall survival (OS) in head and neck squamous cell carcinoma (HNSCC). However, little is known about MAGE in lymph node metastases (LNM) and recurrent disease (RD) of HNSCC.

To assess whether MAGE expression increases with metastasis or recurrence, a tissue microarray (TMA) of 552 primary tumors (PT), 219 LNM and 75 RD was evaluated by immunohistochemistry for MAGE antigens using three monoclonal antibodies to multiple MAGE family members. Mean expression intensity (MEI) was obtained from triplicates of each tumor specimen.

The median MEI compared between PT, LNM and RD was significantly higher in LNM and RD. In paired samples, MEI was comparable in PT to respective LNM, but significantly different from RD. Up to 25% of patients were negative for pan-MAGE or MAGE-A3/A4 in PT, but positive in RD. The prognostic impact of MAGE expression was validated in the TMA cohort and also in TCGA data (mRNA). OS was significantly lower for patients expressing pan-MAGE or MAGE-A3/A4 in both independent cohorts.

MAGE expression was confirmed as a prognostic marker in HNSCC and may be important for immunotherapeutic strategies as a shared antigen.


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