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Angiogenesis and Lymphangiogenesis in Parathyroid Proliferative Lesions

Endocrinology Department (N.G.d.l.T., J.A.H.W., H.E.T.), The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Headington, Oxford OX3 7LJ, United Kingdom; and Histopathology Department (I.B.) and Wetherall Institute of Molecular Medicine (D.G.J.), John Radcliffe Hospital, Headington, Oxford OX3 9DZ, United Kingdom

Address all correspondence and requests for reprints to: Dr. Helen Turner, Department of Endocrinology, The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, Old Road, Headington, Oxford OX3 7LJ, United Kingdom. E-mail: helen.turner{at}orh.nhs.uk.

Angiogenesis and lymphangiogenesis are involved in tumoral growth and metastatic spread. There is little information on angiogenesis and no available data on lymphangiogenesis in parathyroid glands (PTG). Using immunohistochemistry for CD34, LYVE-1 (specific markers for vascular and lymphatic endothelium, respectively), vascular endothelial growth factor (VEGF)-A, VEGF-C, and fibroblast growth factor (FGF)-2, this study analyzes microvascular density (MVD), lymphatic vascular density (LVD), and expression of angiogenic and lymphangiogenic growth factors in 13 normal PTG, 77 parathyroid adenomas (PTA), and 17 primary parathyroid hyperplasia (PPH). MVD was higher in PPH and PTA, compared with PTG (P < 0.001). There was no difference in VEGF-A expression among groups. In contrast, FGF-2 expression was higher in PPH, compared with PTA and PTG (P < 0.0001). FGF-2 scores and MVD were significantly correlated (r = 0.43). LVD did not differ among groups, and VEGF-C expression was unrelated to LVD. There was no relationship between MVD and tumor behavior (adenoma size, PTH, or calcium).

In conclusion, this study shows increased angiogenesis in parathyroid proliferative lesions compared with normal glands and suggests that FGF-2 is proangiogenic in parathyroid tissue. In PTA, tumor behavior is not related to angiogenic phenotype. This is the first demonstration of lymphatic vessels in PTG, but the lack of correlation with VEGF-C expression suggests that VEGF-C is not the primary lymphangiogenic factor.

This work was supported by The Oxford Radcliffe Hospital Charitable Fund (Grant 1057295) and the Novo Nordisk Foundation.

Abbreviations: FGF, Fibroblast growth factor; LVD, lymphatic vascular density; MVD, microvascular density; pHPT, primary hyperparathyroidism; PPH, primary parathyroid hyperplasia; PTA, parathyroid adenoma(s); PTG, parathyroid gland(s); VEGF, vascular endothelial growth factor.

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