MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrences-implications for immunotherapy
Year: 2017
Type: article
Study design: Observational Study
Abstract: // Simon Laban 1 , Gregor Giebel 1 , Niklas Klümper 2 , Andreas Schröck 3 , Johannes Doescher 1 , Giulio Spagnoli 4 , Julia Thierauf 1 , Marie-Nicole Theodoraki 1 , Romain Remark 5 , Sacha Gnjatic 5 , Rosemarie Krupar 2, 6 , Andrew G. Sikora 6 , Geert Litjens 7 , Niels Grabe 7 , Glen Kristiansen 8 , Friedrich Bootz 3 , Patrick J. Schuler 1 , Cornelia Brunner 1 , Johannes Brägelmann 9 , Thomas K. Hoffmann 1, * , Sven Perner 2, * 1 Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany 2 Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Germany 3 Department of Otorhinolaryngology, University Hospital Bonn, Bonn, Germany 4 Department of Biomedicine, University Hospital Basel, Basel, Switzerland 5 Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York City, NY, USA 6 Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA 7 Hamamatsu Tissue Imaging and Analysis Center, BIOQUANT, University of Heidelberg, Heidelberg, Germany 8 Institute of Pathology, University Hospital Bonn, Bonn, Germany 9 Department 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.
Source: Oncotarget
Authors: 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, Sven Perner
Language: English
Topic: Head and Neck Cancer Studies
Subfield: Otorhinolaryngology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W2581557469