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

共聚焦激光扫描显微镜（CLSM）结合免疫组织化学观察IV型胶原的微血管结构清晰可见的三维图像。该方法显示，甲状腺肿瘤的基本血管形态与生长形态密切相关，提示甲状腺肿瘤的实质和间质特征之间存在相互依赖关系。为此，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分析显示，所有甲状腺肿瘤标本均表达了-121、-165和189个氨基酸形式的VEGF条带。Northern blot分析显示，与正常甲状腺样本相比，肿瘤组织中VEGF mRNA水平升高。通过非同位素原位杂交和免疫组化，大多数肿瘤细胞表达VEGF mRNA和蛋白，而VEGF仅在正常甲状腺组织中分离滤泡上皮中表达。血管内皮生长因子在乳头状癌肿瘤乳头上覆的肿瘤细胞和未分化癌坏死周围的肿瘤细胞中表达强烈。我们的研究结果表明，甲状腺肿瘤的组织学类型可能通过涉及VEGF的旁分泌机制决定血管模式。

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.