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摘要:
目的 探讨在正常胸腺、胸腺瘤、胸腺癌组织中titin抗原决定簇的表达及其与重症肌无力(myastheniagravis, MG)临床表现的关系。 方法 选取4例MG伴胸腺瘤患者的胸腺瘤、1例胸腺癌、1例MG伴胸腺瘤患者胸腺瘤旁增生的胸腺组织以及1例正常胸腺组织标本, 对所有标本作连续冰冻切片, 分别进行HE染色、细胞角蛋白(cytokeratin, CK)和titin抗原的免疫组化染色, 同时测定MG伴胸腺瘤患者血清titin抗体的浓度。 结果 免疫组化染色结果显示, titin在胸腺瘤中表达呈强阳性, 其分布与胸腺瘤上皮细胞的分布一致, 胸腺瘤内淋巴细胞和其他结构titin染色呈阴性; 在胸腺癌组织内titin染色呈阴性; 在正常胸腺中titin染色位于胸腺小体, 呈弱阳性, 其他结构未见着色。4例MG伴胸腺瘤患者中有3例血清titin抗体阳性。 结论 MG伴胸腺瘤患者的胸腺瘤组织中有titin抗原决定簇的表达, 且仅表达于胸腺瘤上皮细胞, 而正常胸腺组织中titin表达于胸腺小体, 提示伴MG的胸腺瘤中发生了免疫微环境的变化。 Abstract:Objective To investigate the expression of titin epitope in normal thymus, thymoma, and thymus carcinoma and explore the correlation of titin expression in thymus with the clinical manifestation of myasthenia gravis (MG). Methods Thymoma tissues from four thymoma patients with MG, thymus carcinoma tissue from one patient, hyperplastic thymus tissue from one thymoma patient with MG, and normal thymus tissue from one patient were obtained. Each specimen underwent HE staining and immunohistochemistry staining using anti-cytokeratin (CK) and anti-titin antibodies. Surum anti-titin antibody level of thymoma patients with MG was also examined. Results In MG-associated thymoma, the expression of anti-titin antibody was strongly positive, and its distribution was consistent with that of epithelial cells. However, the lymphocytes and other structures were not stained. In the tissue of thymus carcinoma, the expression of anti-titin antibody was negative. In normal thymus tissue, only the expression of Hassall body was weakly positive, while other structures were not stained. Serum anti-titin antibody was detected in three of the four thymoma patients with MG. Conclusions Titin epitope is expressed only on the epithelial cells in thymoma patients with MG. In normal thymus, titin epitope is expressed only in the area of Hassall bodies. These findings indicate pathogenic change of immune microenvironment in the thymoma patients with MG. -
Key words:
- myasthenia gravis /
- muscle proteins /
- titin /
- thymoma
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图 1 正常胸腺组织染色结果(×20)
A. CK染色可见大量淋巴细胞中有染成黄褐色的上皮细胞，胞浆丰富; B. titin染色可见上皮细胞和胸腺小体以及上皮样细胞，均染为黄褐色，颜色较浅
图 2 胸腺癌组织染色结果(×20)
A. HE染色; B. CK染色可见胸腺癌中肿瘤细胞被染为黄褐色，细胞核漏染; C. titin染色示titin抗原未显色，呈阴性; D.对照为较均匀一致的淡淡背景着色
图 3 胸腺瘤组织连续冰冻切片染色结果(×10)
连续冰冻切片显示同一区域，正上方见一血管，向左下延伸一小叶间隔A. HE染色见小叶间隔下聚集蓝紫色之淋巴细胞丰富区; B. CK染色可见小叶间隔下染色缺失区; C. titin染色亦可见小叶间隔下染色缺失区
图 4 胸腺瘤组织连续冰冻切片染色结果(×10)
连续冰冻切片显示同一区域，左上、左下见肿瘤小叶分隔A. HE染色见中间呈蓝紫色之蝶形区域，淋巴细胞丰富，上皮细胞染为红色; B. CK染色见蝶形染色缺失区，余为染成黄褐色的上皮细胞; C. titin染色亦可见蝶形染色缺失区，余为染成黄褐色的上皮细胞
表 1 患者临床资料及抗体水平
病例 性别 年龄(岁) 病程 诊断 Osserman
分型胸腺病理
诊断及分型AchR抗体 血清titin
抗体前膜 后膜 1 女 47 20d MG伴胸腺瘤 Ⅰ 胸腺瘤上皮型 1.20 1.26 1.73 2 男 65 2个月 MG伴胸腺瘤 ⅡB 胸腺瘤上皮型 1.03 1.40 2.40 3 女 28 2个月 MG伴胸腺瘤 ⅡB 胸腺瘤混合型 1.10 1.16 1.14 4* 男 48 6年 MG伴胸腺瘤 ⅡA 胸腺瘤上皮型 1.00 1.00 2.00 5 女 45 6个月 胸腺癌 － 胸腺癌 － － － 6 男 10 － 骨嗜酸性肉芽肿 － 正常 － － － *取该患者胸腺瘤旁增生的胸腺组织同时进行染色; MG:重症肌无力; － :无或未检测; AchR:乙酰胆碱受体; AchR抗体正常值:突触前膜＜1. 5，突触后膜＜1. 0; titin抗体＞1. 7为阳性 
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