Characteristics of angioarchitecture in thyroid tumors in associated with expression of vascular endothelial growth factor (VEGF)

激光共聚焦扫描显微镜(CLSM)观察结合免疫组织化学IV型胶原清晰地显示了微血管结构的三维图像。该方法显示甲状腺肿瘤的基本血管类型与生长模式有很好的相关性，表明甲状腺肿瘤的实质和间质特征之间存在相互依赖关系。在这方面，我们决定研究血管内皮生长因子(VEGF)在甲状腺肿瘤中的作用。RT-PCR分析表明，所有甲状腺肿瘤标本均表达相应于-121、-165和189氨基酸形式的条带。Northern印迹分析显示，与正常甲状腺组织相比，肿瘤组织中的血管内皮生长因子基因表达水平升高。用非同位素原位杂交和免疫组织化学方法检测，大多数肿瘤细胞表达VEGFmRNA和蛋白，而正常甲状腺组织中仅在分离的滤泡上皮有表达。在乳头状癌的乳头状癌和未分化癌中，VEGF在肿瘤乳头状癌和坏死灶周围的肿瘤细胞中有较强的表达。我们的结果提示，甲状腺肿瘤的组织学类型可能通过涉及血管内皮生长因子的旁分泌机制来决定血管模式。

Confocal laser scanning microscopy (CLSM) observation combined with immunohistochemistry for type IV collagen clearly visualized 3-dimensional images of the microvascular structures. This method revealed that the fundamental vascular pattern correlates well with the growth pattern, suggesting an interdependence between parenchyma and stroma characteristic for thyroid tumors. In this respect, we determined to study vascular endothelial growth factor (VEGF) in thyroid tumors. RT-PCR analysis showed that all specimens of thyroid tumors expressed bands corresponding to -121, -165, and 189-amino acid forms of VEGF. Northern blot analysis showed an increase in VEGF mRNA levels in neoplastic tissues in comparison with normal thyroid samples. By nonisotopic in situ hybridization and immunohistochemistry, most of the tumor cells expressed VEGF mRNA and protein, whereas VEGF expression was identified only in epithelium of isolated follicles in normal thyroid tissues. Intense expression of VEGF was observed in overlying tumor cells of neoplastic papillae of papillary carcinoma and in tumor cells surrounding necrosis in undifferentiated carcinoma. Our results suggest that the histological types of thyroid tumor may determine the vascular pattern through a paracrine mechanism involving VEGF.