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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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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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ORIGINAL ARTICLE
The expression of melanoma-associated antigen A (MAGE-A) in oral
squamous cell carcinoma: an evaluation of the significance
for tumor prognosis
Anna Trippel
1
&Frank Halling
2
&Paul Heymann
2
&Mustafa Ayna
3
&Bilal Al-Nawas
1
&Thomas Ziebart
2
Received: 16 November 2018 /Accepted: 2 May 2019 /Published online: 15 May 2019
#Springer-Verlag GmbH Germany, part of Springer Nature 2019
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 examinesthe hypothesis that MAGE-A is being produced in OSCC but not in mucosa tissue and if MAGE-
A has any correlation to clinical patients 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=0.007andp=0.004).
Patients got distant metastasis and influence of MAGE-A on metastatic behaviorcould 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.
Keywords Squamous cell carcinoma .Cancer .Tumor .Tumor predictor .MAGE
Introduction
In spite of numerous developments in the diagnosis and treat-
ment of oral squamous cell carcinoma, the survival rate of
these patients remains 50% [1]. Concurrently, the number of
newly diagnosed cases increases with a rising tendency [2,3].
One of the most challenging parts is the duly recognition of
the malignancy. Most of the OSCC are diagnosed in an ad-
vanced stadium by which the survival rate can decline to 30%
and lower [4,5]. The standard treatment is the surgical resec-
tion of the tumor. Advanced diseases in stadium III or IV
require a combined-modality treatment consisting of resec-
tion, radiation, and chemotherapy [6,7]. This approach en-
hances the overall survival rate compared to a surgical inter-
vention only, but this progress is still not decisive [8]. The
more important it seems to develop reliable methods for the
identification of early-stage OSCC and to improve the therapy
approach of the advanced diseases for a better overall progno-
sis. Recently, there are a number of examinations concerning
the immunological features of tumors, especially the use of
*Thomas Ziebart
Thomas.ziebart@uk-gm.de
1
Department of Oral and Maxillofacial Surgery University Medical
Center Mainz, Mainz, Germany
2
Department of Oral and Maxillofacial Surgery, Baldingerstrasse,
Philipps University of Marburg, University Hospital Giessen and
Marburg, Campus Marburg, D-35037 Marburg, Germany
3
Center for Dental Implantology, 47051 Duisburg, Germany
Oral and Maxillofacial Surgery (2019) 23:343352
https://doi.org/10.1007/s10006-019-00778-x
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
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