title: Increased expression of pro-angiogenic factors and vascularization in thyroid hyperfunctioning adenomas with and without TSH receptor activating mutations.
abstract: 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.
authors: Department of Health Sciences, University of Catanzaro "Magna Graecia", Viale Europa, Germaneto, 88100, Catanzaro, Italy.
authors: Marilena
authors: M
authors: Celano
authors: Marialuisa
authors: M
authors: Sponziello
authors: Giovanni
authors: G
authors: Tallini
authors: Valentina
authors: V
authors: Maggisano
authors: Rocco
authors: R
authors: Bruno
authors: Mariavittoria
authors: M
authors: Dima
authors: Enrico
authors: E
authors: Di Oto
authors: Adriano
authors: A
authors: Redler
authors: Cosimo
authors: C
authors: Durante
authors: Rosario
authors: R
authors: Sacco
authors: Sebastiano
authors: S
authors: Filetti
authors: Diego
authors: D
authors: Russo
mesh_terms: D042501:Angiogenic Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D006044:Goiter, Nodular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008208:Lymphatic System / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D011989:Receptors, Thyrotropin / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D013961:Thyroid Gland / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013971:Thyrotoxicosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D020033:Protein Isoforms; D012333:RNA, Messenger; D011989:Receptors, Thyrotropin; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor