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

  • 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 cohortMelanoma 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.show moreshow less

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Author:Simon Laban, Gregor Giebel, Niklas Klümper, Andreas Schröck, Johannes DoescherORCiDGND, 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
URN:urn:nbn:de:bvb:384-opus4-1014203
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/101420
ISSN:1949-2553OPAC
Parent Title (English):Oncotarget
Publisher:Impact Journals, LLC
Type:Article
Language:English
Year of first Publication:2017
Publishing Institution:Universität Augsburg
Release Date:2023/01/31
Tag:Oncology
Volume:8
Issue:9
First Page:14719
Last Page:14735
DOI:https://doi.org/10.18632/oncotarget.14830
Institutes:Medizinische Fakultät
Medizinische Fakultät / Universitätsklinikum
Medizinische Fakultät / Lehrstuhl für Hals-, Nasen- und Ohrenheilkunde
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 3.0: Creative Commons - Namensnennung (mit Print on Demand)