de la Torre N Garcia, Buley I, Wass J A H, Turner H E
Servicio de Endocrinología y Nutrición, Hospital Clínico San Carlos, Profesor Martín Lagos s/n, 28040 Madrid, Spain.
Endocr Relat Cancer. 2006 Sep;13(3):931-44. doi: 10.1677/erc.1.01210.
The role of angiogenesis and lymphangiogenesis in thyroid cancer pathogenesis has not been elucidated. Patterns for tumour behaviour and metastasic spread vary according to tumour type and whether differences in the angiogenic or lymphangiogenic phenotype influence the route for tumour metastases or determine a more aggressive behaviour has not been fully explored. The angiogenic and lymphangiogenic phenotypes of a large cohort of thyroid proliferative lesions (n=191) were studied. Using immunohistochemistry for CD34, lymphatic vessel endothelial receptor-1 (LYVE-1) (specific markers for vascular and lymphatic endothelium respectively), vascular endothelial growth factor (VEGF-A), VEGF-C and fibroblast growth factor-2 (FGF-2), this study analyses microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic factors in normal thyroid (NT; n=19), multinodular goitre (n=25), toxic multinodular goitre (n=8), Graves' hyperplasia (n=22), follicular adenoma (n=54), papillary carcinoma (PC; n=27), incidental papillary microcarcinoma (PMC; n=8), follicular carcinoma (FC; n=20) and medullary carcinoma (MC; n=8). MVD was decreased in proliferative lesions, benign and malignant, compared with NT (P<0.0001). In contrast, VEGF-A expression was increased in thyroid carcinomas (PC, FC and MC) when compared with PMC, benign lesions and NT (P<0.0001). LVD was higher in PC and PMC (P=0.001), and VEGF-C expression was increased in PC (P<0.0001). Despite higher LVD and increased expression of VEGF-A and VEGF-C in thyroid cancers, these markers were not related to poor prognosis in terms of tumour size, multifocality and/or presence of lymphatic or distant metastases. In conclusion, angiogenesis is reduced in thyroid proliferative lesions compared with NT tissue. However, VEGF-A expression is upregulated in thyroid cancers. Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to lymphatic metastases. This may be an important mechanism underlying the differences in metastatic behaviour between papillary and follicular thyroid cancer.
血管生成和淋巴管生成在甲状腺癌发病机制中的作用尚未阐明。肿瘤行为和转移扩散模式因肿瘤类型而异，血管生成或淋巴管生成表型的差异是否会影响肿瘤转移途径或决定更具侵袭性的行为尚未得到充分研究。本研究对一大组甲状腺增殖性病变（n = 191）的血管生成和淋巴管生成表型进行了研究。使用针对CD34、淋巴管内皮受体-1（LYVE-1）（分别为血管和淋巴管内皮的特异性标志物）、血管内皮生长因子（VEGF-A）、VEGF-C和成纤维细胞生长因子-2（FGF-2）的免疫组织化学方法，本研究分析了正常甲状腺（NT；n = 19）、结节性甲状腺肿（n = 25）、毒性结节性甲状腺肿（n = 8）、格雷夫斯增生（n = 22）、滤泡性腺瘤（n = 54）、乳头状癌（PC；n = 27）、偶然发现的乳头状微小癌（PMC；n = 8）、滤泡癌（FC；n = 20）和髓样癌（MC；n = 8）中的微血管密度（MVD）、淋巴管密度（LVD）以及血管生成和淋巴管生成因子的表达。与NT相比，增殖性病变（良性和恶性）中的MVD降低（P < 0.0001）。相反，与PMC、良性病变和NT相比，甲状腺癌（PC、FC和MC）中的VEGF-A表达增加（P < 0.0001）。PC和PMC中的LVD较高（P = 0.001），PC中的VEGF-C表达增加（P < 0.0001）。尽管甲状腺癌中的LVD较高且VEGF-A和VEGF-C表达增加，但这些标志物在肿瘤大小、多灶性和/或存在淋巴或远处转移方面与不良预后无关。总之，与NT组织相比，甲状腺增殖性病变中的血管生成减少。然而，甲状腺癌中VEGF-A表达上调。在易于发生淋巴转移的甲状腺肿瘤中，淋巴管生成和VEGF-C表达增加。这可能是甲状腺乳头状癌和滤泡癌转移行为差异的重要潜在机制。
