TY - JOUR
T1 - MAGE expression in head and neck squamous cell carcinoma primary tumors, lymph node metastases and respective recurrencesimplications for immunotherapy
AU - Laban, Simon
AU - Giebel, Gregor
AU - Klümper, Niklas
AU - Schröck, Andreas
AU - Doescher, Johannes
AU - Spagnoli, Giulio
AU - Thierauf, Julia
AU - Theodoraki, Marie Nicole
AU - Remark, Romain
AU - Gnjatic, Sacha
AU - Krupar, Rosemarie
AU - Sikora, Andrew G.
AU - Litjens, Geert
AU - Grabe, Niels
AU - Kristiansen, Glen
AU - Bootz, Friedrich
AU - Schuler, Patrick J.
AU - Brunner, Cornelia
AU - Brägelmann, Johannes
AU - Hoffmann, Thomas K.
AU - Perner, Sven
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Cancer-testis antigens
KW - HNSCC
KW - Head and neck squamous cell carcinoma
KW - MAGE
KW - Melanoma-associated antigen
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U2 - 10.18632/oncotarget.14830
DO - 10.18632/oncotarget.14830
M3 - Article
C2 - 28146422
AN - SCOPUS:85014118691
SN - 1949-2553
VL - 8
SP - 14719
EP - 14735
JO - Oncotarget
JF - Oncotarget
IS - 9
ER -