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 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.
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Simon
S
Laban
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Gregor
G
Giebel
Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Germany.
Niklas
N
Klümper
Department of Otorhinolaryngology, University Hospital Bonn, Bonn, Germany.
Andreas
A
Schröck
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Johannes
J
Doescher
Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Giulio
G
Spagnoli
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Julia
J
Thierauf
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Marie-Nicole
MN
Theodoraki
Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York City, NY, USA.
Romain
R
Remark
Department of Medicine, Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, Mount Sinai Hospital, New York City, NY, USA.
Sacha
S
Gnjatic
Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Germany.|Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Rosemarie
R
Krupar
Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Andrew G
AG
Sikora
Hamamatsu Tissue Imaging and Analysis Center, BIOQUANT, University of Heidelberg, Heidelberg, Germany.
Geert
G
Litjens
Hamamatsu Tissue Imaging and Analysis Center, BIOQUANT, University of Heidelberg, Heidelberg, Germany.
Niels
N
Grabe
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Glen
G
Kristiansen
Department of Otorhinolaryngology, University Hospital Bonn, Bonn, Germany.
Friedrich
F
Bootz
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Patrick J
PJ
Schuler
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Cornelia
C
Brunner
Department of Oncology, University Hospital Bonn, Bonn, Germany.
Johannes
J
Brägelmann
Department of Oto-Rhino-Laryngology and Head and Neck Surgery, Head and Neck Cancer Center Ulm, University Medical Center Ulm, Ulm, Germany.
Thomas K
TK
Hoffmann
Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Germany.
Sven
S
Perner
D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D007150:Immunohistochemistry; D007167:Immunotherapy / Q000379:methods*; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008297:Male; D058950:Melanoma-Specific Antigens / Q000235:genetics / Q000378:metabolism*; D015999:Multivariate Analysis; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009364:Neoplasm Recurrence, Local; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; C072013:MAGEA3 protein, human; C095204:MAGEA4 protein, human; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D012333:RNA, Messenger
HNSCC; MAGE; cancer-testis antigens; head and neck squamous cell carcinoma; melanoma-associated antigen