Chen Yao-Tseng, Hsu Melinda, Lee Peishan, Shin Sandra J, Mhawech-Fauceglia Paulette, Odunsi Kunle, Altorki Nasser K, Song Chao-Jun, Jin Bo-Quan, Simpson Andrew J, Old Lloyd J
Departments of Pathology and Surgery, Weill Cornell Medical College, New York, NY 10065, USA.
Int J Cancer. 2009 Jun 15;124(12):2893-8. doi: 10.1002/ijc.24296.
CT45 is a cancer/testis gene that we previously identified by massively parallel signature sequencing. Encoded by a multigene family on chromosome X, CT45 showed restricted mRNA expression to normal testis and various cancers. In this study, monoclonal antibodies were generated against recombinant CT45 protein, and CT45 protein expression in normal and tumor tissues was evaluated by immunohistochemical analysis. In adult normal tissue, CT45 expression was restricted to testicular germ cells, detected as a nuclear protein mainly at the stage of primary spermatocytes. In tumors, CT45 protein expression correlated with the mRNA levels detected by quantitative RT-PCR, and most lung cancer and ovarian cancers with CT45 mRNA at levels >1% of testicular expression were CT45 protein-positive. In positive cases, CT45 showed expression patterns that ranged from diffuse strong staining to heterogeneous and patchy expression. In lung cancer, CT45 expression was least frequent in adenocarcinoma, more frequent in squamous cell carcinoma and neuroendocrine tumors. Using tissue microarrays, 376 lung cancer, 219 ovarian cancer and 155 breast cancer were evaluated for CT45 protein expression. The expression frequency was highest in ovarian cancer (37%), followed by lung cancer (13%) and lowest in breast cancer (<5%). Given the focal nature of CT45 expression in many cases, these numbers represented the minimal frequency of expression in these tumor types. In summary, the expression frequency and characteristics of CT45 expression are similar to other CT cancer vaccine targets currently in clinical trials, e.g., NY-ESO-1 and MAGE-A, suggesting CT45 as a potentially useful cancer target.
CT45是一种癌症/睾丸基因，我们之前通过大规模平行签名测序鉴定出该基因。CT45由X染色体上的一个多基因家族编码，其mRNA表达仅限于正常睾丸和各种癌症。在本研究中，我们制备了针对重组CT45蛋白的单克隆抗体，并通过免疫组织化学分析评估了CT45蛋白在正常组织和肿瘤组织中的表达情况。在成人正常组织中，CT45表达仅限于睾丸生殖细胞，主要在初级精母细胞阶段被检测为一种核蛋白。在肿瘤中，CT45蛋白表达与定量逆转录聚合酶链反应检测到的mRNA水平相关，大多数CT45 mRNA水平>睾丸表达1%的肺癌和卵巢癌为CT45蛋白阳性。在阳性病例中，CT45表现出从弥漫性强染色到异质性和斑片状表达的表达模式。在肺癌中，CT45表达在腺癌中最少见，在鳞状细胞癌和神经内分泌肿瘤中更常见。使用组织芯片对376例肺癌、219例卵巢癌和155例乳腺癌进行了CT45蛋白表达评估。表达频率在卵巢癌中最高（37%），其次是肺癌（13%），在乳腺癌中最低（<5%）。鉴于在许多情况下CT45表达具有局灶性，这些数字代表了这些肿瘤类型中最小的表达频率。总之，CT45的表达频率和特征与目前正在进行临床试验的其他CT癌症疫苗靶点（如NY-ESO-1和MAGE-A）相似，表明CT45是一个潜在有用的癌症靶点。
