Fujita Shoichiro, Wada Hisashi, Jungbluth Achim A, Sato Shuichiro, Nakata Tetsuya, Noguchi Yuji, Doki Yuichiro, Yasui Masayoshi, Sugita Yurika, Yasuda Takushi, Yano Masahiko, Ono Toshiro, Chen Yao-Tseng, Higashiyama Masahiko, Gnjatic Sacha, Old Lloyd J, Nakayama Eiichi, Monden Morito
Department of Surgery and Clinical Oncology, Graduate School of Medicine, Osaka University, Osaka, Japan.
Clin Cancer Res. 2004 Oct 1;10(19):6551-8. doi: 10.1158/1078-0432.CCR-04-0819.
Although NY-ESO-1 was isolated from an esophageal carcinoma patient, its expression in this type of cancer and its immunogenicity in esophageal cancer patients have not yet been fully elucidated. We report here the frequency of NY-ESO-1 mRNA and protein expression in esophageal cancer and the presence of NY-ESO-1-specific immune response in patients.
One hundred twenty three esophageal squamous cell carcinoma specimens were analyzed for the expression of NY-ESO-1 mRNA by conventional and real-time reverse transcription-PCR and the expression of protein by immunohistochemistry and Western blot. Sera and peripheral blood lymphocytes from 51 patients were analyzed for the NY-ESO-1 antibody production by enzyme-linked immunosorbent assay and NY-ESO-1 T cell response by enzyme-linked immunospot assay. Survival analyses were also performed.
NY-ESO-1 mRNA was expressed in 41 of 123 (33%) esophageal squamous cell carcinoma specimens, and its expression was found at higher frequency in well-differentiated and moderately differentiated type of cancer. No mRNA copy was detected in any of the adjacent normal tissues. Twenty-one of 24 (87.5%) NY-ESO-1 mRNA-positive tumors were stained positively by immunohistochemistry. Correlation between the level of NY-ESO-1 mRNA expression and the degree of immunohistochemistry positivity was observed. Antibody production was observed in 2 patients with tumors that showed protein expression. Furthermore, a CD8 T-cell response against NY-ESO-1 was observed in 1 of the 2 seropositive patients.
The high expression frequency of NY-ESO-1 mRNA and protein indicates NY-ESO-1 as a feasible vaccine target in esophageal cancer.
尽管NY - ESO - 1是从一名食管癌患者中分离出来的,但其在这类癌症中的表达及其在食管癌患者中的免疫原性尚未完全阐明。我们在此报告食管癌中NY - ESO - 1 mRNA和蛋白表达的频率以及患者中NY - ESO - 1特异性免疫反应的存在情况。
采用传统和实时逆转录 - PCR分析123例食管鳞状细胞癌标本中NY - ESO - 1 mRNA的表达,采用免疫组织化学和蛋白质印迹法分析蛋白表达。采用酶联免疫吸附测定法分析51例患者血清和外周血淋巴细胞中NY - ESO - 1抗体的产生情况,采用酶联免疫斑点测定法分析NY - ESO - 1 T细胞反应。还进行了生存分析。
123例食管鳞状细胞癌标本中有41例(33%)表达NY - ESO - 1 mRNA,其在高分化和中分化型癌症中的表达频率更高。在任何相邻正常组织中均未检测到mRNA拷贝。24例NY - ESO - 1 mRNA阳性肿瘤中有21例(87.5%)免疫组织化学染色呈阳性。观察到NY - ESO - 1 mRNA表达水平与免疫组织化学阳性程度之间的相关性。在2例有蛋白表达的肿瘤患者中观察到抗体产生。此外,在2例血清阳性患者中的1例中观察到针对NY - ESO - 1的CD8 T细胞反应。
NY - ESO - 1 mRNA和蛋白的高表达频率表明NY - ESO - 1是食管癌中一个可行的疫苗靶点。