Expression of MAGE gene in esophageal carcinomas and its clinical application

MAGE基因家族在部分食管鳞状细胞系中的表达频率为67%~22%(MAGE-1.67%；MAGE-2.22%；MAGE-3.33%：MAGE-3/6.78%；MAGE-4/41.44%)。65例食管鳞癌中MAGE基因家族的表达频率分别为19%、26%、2%、5%和8%。在转移阳性的淋巴结中，MAGE-1和MAGE-2基因表达阳性，发生率分别为46%和18%。并将MAGE基因表达与临床病理结果进行对照研究。本研究发现肿瘤低侵袭性与高侵袭性、0-II期与III-IV期有显著差异，MAGE基因表达与术后生存期无统计学差异。用自制的抗MAGE-1和抗MAGE-4的单抗对部分食管癌细胞系和冰冻标本进行免疫组织化学染色。免疫印迹分析显示两种抗体均有较好的反应，但抗MAGE-1单抗与血样反应较差。因此，用抗MAGE-4单抗和多克隆抗体制作了抗MAGE-4的ELISA试剂盒。在用正常人检测MAGE-4蛋白浓度时，多数病例的MAGE-4值小于1.0 ng/ml，据此以1.15 ng/ml为临界值，以2SD水平作为临界值。38例食管鳞癌中，MAGE-4阳性8例，阳性率为21%。治疗前后预后良好的患者血清MAGE-4蛋白水平明显降低。虽然我们尝试用重组MAGE蛋白来诱导肿瘤特异性细胞毒性T淋巴细胞，但由于没有诱导肿瘤特异性T淋巴细胞，本研究失败了。

MAGE gene family was expressed in some esophageal squamous cell lines with an incidence of 67% to 22% (MAGE-1.67% ; MAGE-2.22% ; MAGE-3.33% : MAGE-3/6.78% ; and MAGE-4/41.44%), while in 65 patients with esophageal squamous cell cancer the incidence was 19%, 26%, 2%, 5%, and 8%, respectively. In the lymph nodes with positive metastasis, gene expression was recognized in MAGE-1 and -2 with an incidence rate was 46% and 18%, respectively. A comparative study was also done between MAGE gene expression and clinicopathologic findings. By this study, a significant difference was found between the tumor invasion low and high, and staging 0-II and III-IV.There was no statistical significant difference between the expression of MAGE gene and postoperative survivals. Immunohistochemistry using anti-MAGE-1 and anti-MAGE-4 monoclonal antibody which were made by our institution, was performed to some cell lines and frozen specimens of the esophageal cancer. Both antibodies showed a good reaction in Western blotting analysis, but anti-MAGE-1 monoclonal antibody poorly reacted to the flesh specimens. Therefore, ELISA kit was made using ant-mage-4 monoclonal and polyclonal antibodies. In the analyzes of MAGE-4 protein concentration using normal cases, most cases showed the MAGE-4 values of less than 1.0 ng/ml. By this result, the cut-off line was set at 1.15ng/ml with a 2S.D.level. In patients with squamous cell carcinoma of the esophagus, MAGE-4 positive was found in 8 of 38 cases, with an incidence of 21%. Clear reductions in serum MAGE-4 protein was found in cases with good prognosis before and after curative esophagectyomy. Although we attempted to induce tumor specific cytotoxic T lymphocytes using recombinant MAGE proteins, this study was failed because tumor specific T lymphocytes were not induced.