MAGE-A proteins are highly expressed in oral squamous cell carcinoma (OSCC) and are promising targets for cancer immunotherapy. This study examined the presence of MAGE-A expression within the tumor center (TC) and tumor invasive front (TIF) and evaluated its relationship to poor prognosis. The expression rate of each MAGE-A subtype, A1-A12, was examined in 68 OSCCs at the TIF and TC. Slides (1-µm) of tissue microarrays (diameter =0.6 mm) were immunohistochemically stained, and the findings were correlated to clinical data. Approximately 95% of the tumors had MAGE-A expression. Higher expression in the TC was shown significantly for MAGE-A1, -A5, -A6, -A9 and -A12 (P<0.05). MAGE-A2 and -A3 exhibited the opposite behavior (not significant, P>0.05). Age, tumor size, grade and survival time were not associated with the expression of certain MAGE-A subgroups. When expression in the whole tumor tissue was considered, only MAGE-A1 was expressed at a significantly higher rate in male patients (P=0.034). At the TIF, MAGE-A9 and the UICC disease stage were significantly correlated (P=0.0263), and MAGE-A6 and the UICC disease stage exhibited a strong trend (P=0.0596). The expression of MAGE-A3, -A4, -A5, -A9 and -A11 was significantly associated with lymph node metastasis, while MAGE-A4 was expressed in all regions of the tumors (TIF and TC). This study showed that higher expression of most MAGE-A antigens occurred at the TC rather than at the TIF. MAGE‑A1, -A3, -A4, -A5, -A9 and -A11 were significantly associated with clinically advanced stages of disease and seem to be of particular interest.

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Abstract. There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma.

Abstract. Radiotherapy alone, or as an addition to surgery is important for the treatment of head and neck squamous cell carcinoma (HNSCC). In addition to their expression in germ cells, melanoma associated antigens-A (MAGE-A) are only expressed in malignant tissue. Notably, there is a known correlation between MAGE-A9 expression and poor prognosis in HNSCC patients. However, current knowledge regarding the function of MAGE-A9 expression, particularly in the context of irradiation, is limited. MAGE-A9 expression in 37 oral squamous cell carcinoma patents was immunohistochemically determined and analyzed for overall survival by the Kaplan-Meier log-rank test. Next, the expression of MAGE-A9 was determined by reverse transcription-quantitative polymerase chain reaction in HNSCC cell lines prior to and following irradiation with 2 Gray. The radiosensitivity of each cell line was determined using a clonogenic survival assay. There was a significantly (P=0.0468) longer overall survival in patients with a low level of MAGE-A9 expression. The median overall survival in patients with high MAGE-A9 expression was 47% compared to 73% in the group with low MAGE-A9 expression. The cell lines revealed a distinct expression pattern of MAGE-A9. Following irradiation of the cell lines, a significant enhancement of MAGE-A9 mRNA expression levels was observed. The most prominent alteration in MAGE-A9 expression was observed in the most radioresistant cell line. A high MAGE-A9 expression level correlates significantly with lower overall survival in HNSCC patients. Additionally, irradiation increased the MAGE-A9 mRNA levels in all five HNSCC cell lines, and the most resistant cell line demonstrated the greatest increase in MAGE-A9 expression following irradiation.