Endocrine Abstracts (2004) 7 P27

Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour

N Garcia de la Torre1, I Buley2, JAH Wass1, DG Jackson3 & HE Turner1

1Endocrinology Department. The Oxford Centre for Diabetes, Endocrinology and Metabolism. Churchill Hospital, Headington, Oxford, UK; 2Histopathology Department, John Radcliffe Hospital, Headington, Oxford, UK; 3Wetherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, UK.

Background: Angiogenesis and lymphangiogenesis are involved in growth and metastatic spread of tumours. Vascular endothelial growth factor-A (VEGF-A) and fibroblast growth factor-2 (FGF-2) play a key role in angiogenesis through proliferation of endothelial cells. VEGF-C has been identified as the molecular link between tumour lymphangiogenesis and metastasic spread.

Objective: To (1) analyse microvascular density (MVD) and lymphatic vascular density (LVD) using CD34 and LYVE-1 staining (specific markers for vascular and lymphatic endothelial cells respectively), in thyroid proliferative lesions; (2) assess whether this correlates with tumour behaviour; (3) investigate the expression of angiogenic and lymphangiogenic factors in thyroid tissue.

Methods: Immunohistochemistry for CD34, LYVE-1, VEGF-A, VEGF-C, and FGF-2 was performed in normal thyroid (NT, 19), multinodular goitre (25), toxic multinodular goitre (8), hyperplasia (22), follicular adenoma (54), papillary carcinoma (PC, 27), incidental papillary microcarcinoma (PMC, 8), follicular carcinoma (FC, 20), and medullary carcinoma (MC, 8).

Results: MVD was decreased in proliferative lesions, benign and malignant, compared to NT (P<0.0001). In contrast, VEGF-A expresion was increased in thyroid carcinomas (PC, FC, MC) compared to PMC, benign lesions and NT (P<0.0001). FGF-2 expression was not different among groups. LVD was increased in PC, PMC, and MC (P=0.001); and VEGF-C expression was higher in PC and MC (P<0.0001). Despite a higher LVD and increased expression of VEGF-A and VEGF-C in thyroid cancers, these are not markers of poorer prognosis regarding tumoral size, multifocality and/or presence of lymphatic or distant metastasis.

Conclusions: In contrast to common neoplasms and parathyroid tumours, but similar to pituitary tumours, angiogenesis is reduced in thyroid proliferative lesions compared with normal tissue. VEGF-A expression is upregulated in thyroid cancers. Lymphangiogenesis and VEGF-C expression are increased in thyroid tumours prone to lymphatic metastasis (PC, MC). This may be an important mechanism underlying the differences in metastatic behaviour between papillary and follicular thyroid cancer.

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