Lee S S, Park W Y, Chi J G, Seo J W, Kim J I, Kim C W, Park S H, Khang S K, Cho K J, Seo J S, Jang J J
Department of Pathology, Seoul National University College of Medicine, Chongno-gu, Korea.
Virchows Arch. 1998 Jan;432(1):33-42. doi: 10.1007/s004280050131.
There have been several reports that thymoma in human is a progressive disease, and that thymoma and thymic carcinoma form a continuum. We established a stable line of SV40T transgenic mice, which consistently produced thymic epithelial tumours progressing to thymic carcinoma within a predictable time span. Using this animal model and a morphological approach, thymic epithelial tumour progression was studied with reference to sequential changes at different time points in animals aged from 3 to 32 weeks. At all ages, SV40T was expressed in the nuclei of thymic epithelial cells; in these transgenic mice we observed the entire spectrum from cortical type thymoma to thymic carcinoma. Thymic size tended to increase with ageing in SV40T TG mice. While younger mice had predominantly cortical (organoid) or cortical thymoma, older mice had well-differentiated thymic carcinoma (WDTC) or poorly differentiated thymic carcinoma. When SV40T TG mice (248 line) reached a certain age, carcinoma of the thymus was present in all of them. Cortical-type thymoma became malignant within a predictable time span, suggesting a cortical thymoma-carcinoma sequence. When the mice were 9 weeks of age, the thymuses formed gross masses compatible with cortical thymoma. At 14 weeks of age, WDTC appeared against the background of cortical thymoma. Poorly differentiated thymic carcinoma was found after 15 weeks and affected all animals over 23 weeks of age. Most thymic carcinomas coexisted in varying proportions with cortical-type thymoma. Medullary thymomas did not develop in the mice, and no transition from medullary-type thymomas to thymic carcinomas was observed. In this SV40T transgenic mouse model, thymic carcinoma is clearly preceded by cortical-type thymoma. These transgenic mice may provide an interesting model for the progression from cortical thymoma to WDTC and/or high-grade carcinoma.
已有多篇报道称人类胸腺瘤是一种进行性疾病，且胸腺瘤和胸腺癌构成一个连续统一体。我们建立了一种稳定的SV40T转基因小鼠品系，该品系在可预测的时间范围内持续产生进展为胸腺癌的胸腺上皮肿瘤。利用这个动物模型和形态学方法，参照3至32周龄动物不同时间点的连续变化，研究了胸腺上皮肿瘤的进展情况。在所有年龄段，SV40T均在胸腺上皮细胞的细胞核中表达；在这些转基因小鼠中，我们观察到了从皮质型胸腺瘤到胸腺癌的整个谱系。SV40T转基因小鼠的胸腺大小倾向于随年龄增长而增加。年幼小鼠主要为皮质型（类器官型）或皮质胸腺瘤，而年长小鼠则为高分化胸腺癌（WDTC）或低分化胸腺癌。当SV40T转基因小鼠（248品系）达到一定年龄时，所有小鼠均出现胸腺癌。皮质型胸腺瘤在可预测的时间范围内发生恶变，提示存在皮质胸腺瘤-癌序列。当小鼠9周龄时，胸腺形成与皮质胸腺瘤相符的大体肿块。14周龄时，在皮质胸腺瘤背景下出现WDTC。15周后发现低分化胸腺癌，且所有23周龄以上的动物均受影响。大多数胸腺癌与皮质型胸腺瘤以不同比例共存。小鼠未发生髓质胸腺瘤，也未观察到从髓质型胸腺瘤向胸腺癌的转变。在这个SV40T转基因小鼠模型中，胸腺癌显然先于皮质型胸腺瘤出现。这些转基因小鼠可能为从皮质胸腺瘤进展为WDTC和/或高级别癌提供一个有趣的模型。
