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The expression of melanoma-associated antigen A (MAGE-A) in oral squamous cell carcinoma: an evaluation of the significance for tumor prognosis

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Abstract

Objectives

Melanoma-associated antigens A had been detected repeatedly in oral squamous cell carcinoma, but not in healthy mucosa. Additionally, patients with MAGE-A expressing cancers are regarded to have a worse survival prognosis, so that MAGE-A are supposed to be part of carcinogenesis. Which role these antigens fulfill within OSCC is still, up today, largely unknown. This study examines the hypothesis that MAGE-A is being produced in OSCC but not in mucosa tissue and if MAGE-A has any correlation to clinical patient’s parameters like tumor size, lymph node metastasis, distant metastasis, overall survival, and recurrence.

Materials and methods

For this purpose, 50 tumor samples and 39 mucosa samples were analyzed by means of PCR and immunohistochemical staining with the antibody 6C1.

Results

Forty of 41 stained tumor samples showed a positive antibody reaction with a maximum staining rate of 53%. Sixteen mucosa samples showed a mild positive reaction. The PCR revealed a linear expression pattern of MAGE-A in which the genes are proportionally expressed in OSCC. We did not find any relationship between MAGE-A and tumor size, overall survival, or recurrence. There was also no connection between MAGE-A and tumor parameters Hif-1 and LDH. Their expression was detected tendentially in tumors with higher staging, advanced lymph node metastasis, and rising age of the patients. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis (p = 0.007 and p = 0.004). Patients got distant metastasis and influence of MAGE-A on metastatic behavior could not be verified. The genes MAGE-A3 and -A4 are consequently qualified as tumor markers in the field of diagnosis and follow-up of OSCC.

Conclusions and clinical relevance

Two genes have great potential as target proteins in immunotherapy. The genes MAGE-A3+6 and MAGE-A4 had a statistically significant correlation with lymph node metastasis.

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Acknowledgements

We wish to thank Dr. Jutta Goldschmitt for technical support.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery University Medical Center Mainz, Mainz, Germany

    Anna Trippel & Bilal Al-Nawas

  2. Department of Oral and Maxillofacial Surgery, Baldingerstrasse, Philipps University of Marburg, University Hospital Giessen and Marburg, Campus Marburg, D-35037, Marburg, Germany

    Frank Halling, Paul Heymann & Thomas Ziebart

  3. Center for Dental Implantology, 47051, Duisburg, Germany

    Mustafa Ayna

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  1. Anna Trippel
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Contributions

A.S., T.Z., M.A., P.H., and B.A. performed the experiments and analyzed the data. A.S., T.Z., and F.H. wrote the paper. A.S. and T.Z. provided clinical information about patients and treatments. P.H. and M.A. helped in the discussion. B.A. and T.Z. designed the study, analyzed the data, and guided the research presented.

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Correspondence to Thomas Ziebart.

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The authors declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The local ethics committee (Landesärztekammer Rheinland-Pfalz) approved the following experiments (Ethikvotum 837.837.11 (7924)). This article does not contain any studies with animals performed by any of the authors.

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Trippel, A., Halling, F., Heymann, P. et al. The expression of melanoma-associated antigen A (MAGE-A) in oral squamous cell carcinoma: an evaluation of the significance for tumor prognosis. Oral Maxillofac Surg 23, 343–352 (2019). https://doi.org/10.1007/s10006-019-00778-x

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