Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations

Autor: Valentina Maggisano, Enrico Di Oto, Adriano Redler, Rocco Bruno, Cosimo Durante, Giovanni Tallini, Diego Russo, Rosario Sacco, Sebastiano Filetti, Marilena Celano, Marialuisa Sponziello, Mariavittoria Dima
Přispěvatelé: Celano M., Sponziello M., Tallini G., Maggisano V., Bruno R., Dima M., Di Oto E., Redler A., Durante C., Sacco R., Filetti S., Russo D.
Jazyk: angličtina
Rok vydání: 2013
Předmět:
CD31
Vascular Endothelial Growth Factor A
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Thyroid Gland
chemistry.chemical_compound
angiogenesis
Endocrinology
tsh receptor mutations
enos
Protein Isoforms
TSH mutation
Receptors
Platelet-Derived Growth Factor
pdgf
Angiogenic Proteins
Receptor
vegf
Platelet-Derived Growth Factor
biology
Neovascularization
Pathologic
Thyroid
thyroid toxic adenomas
Receptors
Thyrotropin
Neoplasm Proteins
Up-Regulation
Vascular endothelial growth factor
Lymphatic system
medicine.anatomical_structure
Thyrotoxicosis
thyroid nodule
Platelet-derived growth factor receptor
Goiter
Nodular
medicine.medical_specialty
Nitric Oxide Synthase Type III
Lymphatic System
Thyroid peroxidase
Internal medicine
medicine
Humans
hyperthyroidism
RNA
Messenger
Cell Proliferation
Receptors
Vascular Endothelial Growth Factor
chemistry
Microvessels
Mutation
biology.protein
Thyroglobulin
Biomarkers
Popis: Autonomously functioning thyroid nodules (AFTN) are known to receive an increased blood influx necessary to sustain their high rate of growth and hormone production. Here, we investigated the expression of hematic and lymphatic vases in a series of 20 AFTN compared with the contralateral non-tumor tissues of the same patients, and the transcript levels of proteins involved in the control of vascular proliferation, including the vascular endothelial growth factor (VEGF) and platelet-derived growth factors (PDGF) and their receptors and the endothelial nitric oxide synthase (eNOS). In parallel, the expression of the differentiation markers sodium/iodide symporter (NIS), thyroperoxidase (TPO), thyroglobulin (Tg), and TSH receptor (TSHR) was also investigated. The data were further analyzed comparing subgroups of tumors with or without mutations in the TSHR gene. Analysis by means of CD31 and D2-40 immunostaining showed in AFTN an increased number of hematic, but not lymphatic, vessels in parallel with an enhanced proliferation rate shown by increased Ki67 staining. Quantitative RT-PCR analysis revealed an increase of VEGF, VEGFR1 and 2, PDGF-A, PDGF-B, and eNOS expression in tumor versus normal tissues. Also, higher transcript levels of NIS, TPO, and Tg were detected. Comparison of the two subgroups of samples revealed only few differences in the expression of the genes examined. In conclusion, these data demonstrate an increased expression of angiogenesis-related factors associated with an enhanced proliferation of hematic, but not lymphatic, vessels in AFTNs. In this context, the presence of TSHR mutations may only slightly influence the expression of pro-angiogenic growth factors.
Databáze: OpenAIRE
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