Prasad Manju L, Jungbluth Achim A, Patel Snehal G, Iversen Kristin, Hoshaw-Woodard Stacy, Busam Klaus J
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Head Neck. 2004 Dec;26(12):1053-7. doi: 10.1002/hed.20112.
Cancer testis antigens (CTAs) are T-cell-defined tumor-associated antigens encoded by the genes and gene families such as MAGE, NY-ESO-1, and others. Their expression in a wide variety of malignant neoplasms but absence in all normal adult tissue except testicular germ cells makes them attractive targets for immunotherapy of cancer. Primary mucosal melanomas of the head and neck (HNMM) are rare aggressive malignant tumors that are usually difficult to treat. CTAs may provide useful targets for therapy; however, their expression in HNMM is not known.
We analyzed 40 initial, 15 recurrent, and 15 metastatic HNMM to nonmucosal locations from 64 patients (oral, n = 30; sinonasal, n = 34). Immunohistochemistry was performed on archival tissue with monoclonal antibodies 57B, CT7-33, and ES121 to the following CTAs: MAGE-A4, CT7 (MAGE-C1), and NY-ESO-1, respectively.
CT7, MAGE-A4, and NY-ESO-1 expression was seen in 73%, 61%, and 24% of tumors, respectively, with 81% of the tumors expressing at least one of the CTAs. CT7 and MAGE-A4 were significantly more frequently expressed in tumors composed of epithelioid cells than spindle cells (p = .05). CTA expression did not correlate with disease progression, overall survival, and disease-specific survival.
CT7, MAGEA4, and NY-ESO-1 are frequently expressed in HNMM and may be potential targets for CTA-based immunotherapy. The expression does not seem to have prognostic significance.
癌睾丸抗原(CTA)是由MAGE、NY-ESO-1等基因和基因家族编码的T细胞定义的肿瘤相关抗原。它们在多种恶性肿瘤中表达,但在除睾丸生殖细胞外的所有正常成人组织中均不存在,这使其成为癌症免疫治疗的有吸引力的靶点。头颈部原发性黏膜黑色素瘤(HNMM)是罕见的侵袭性恶性肿瘤,通常难以治疗。CTA可能为治疗提供有用的靶点;然而,它们在HNMM中的表达尚不清楚。
我们分析了来自64例患者(口腔,n = 30;鼻窦,n = 34)的40例初发、15例复发和15例转移至非黏膜部位的HNMM。用分别针对以下CTA的单克隆抗体57B、CT7-33和ES121对存档组织进行免疫组织化学分析:MAGE-A4、CT7(MAGE-C1)和NY-ESO-1。
CT7、MAGE-A4和NY-ESO-1的表达分别见于73%、61%和24%的肿瘤,81%的肿瘤表达至少一种CTA。CT7和MAGE-A4在由上皮样细胞组成的肿瘤中比梭形细胞肿瘤中表达更频繁(p = 0.05)。CTA表达与疾病进展、总生存期和疾病特异性生存期无关。
CT7、MAGEA4和NY-ESO-1在HNMM中频繁表达,可能是基于CTA的免疫治疗的潜在靶点。这种表达似乎没有预后意义。