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01-02-2010

Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders

Authors: Asako Itoh, Katsumi Iwase, Shin Jimbo, Haruo Yamamoto, Naoki Yamamoto, Masahiro Kokubo, Takao Senda, Akira Nakai, Akio Nagagasaka, Takaaki Nagasaka, Yatsuka Hibi, Teppei Seko

Published in: World Journal of Surgery | Issue 2/2010

Abstract

Background

Vascular endothelial growth factor (VEGF) is involved in tumor angiogenesis and other pathophysiological processes.

Materials and methods

We studied the localization of VEGF in human thyroid tissues to clarify its involvement in proliferative processes in a variety of thyroid disorders. Immunohistochemical analysis using purified rabbit polyclonal anti-human VEGF or anti-human CD34 antibody and a streptavidin–biotin peroxidase complex detection system was performed on 58 tissue specimens from 53 patients with different thyroid disorders and 5 normal thyroid glands.

Results

Vascular endothelial growth factor was not detected in normal thyroid follicular cells. However, some thyroid tumor cells expressed VEGF in the cytoplasm (papillary carcinoma, 10/18; follicular carcinoma, 1/3; medullary carcinoma, 2/2; follicular adenoma, 3/11; adenomatous goiter, 2/4). In benign follicular adenoma and adenomatous goiter, weak expression of VEGF was found in small areas of the tumor, whereas in malignant thyroid tumors, it was strongly expressed in many cells. However, VEGF was not expressed in anaplastic carcinoma, malignant lymphoma, or Graves’ disease. Angiovascular cells stained with CD34 antibody in tissues from different thyroid disorders reflected statistically significant differences in papillary carcinoma, follicular adenoma, and Graves’ disease compared with normal thyroids, and such cells showed a trend toward increases in medullary carcinoma and adenomatous goiter. In contrast, low vascularity was observed in anaplastic carcinoma, malignant lymphoma, and follicular carcinoma.

Conclusions

Because VEGF probably functions as a hypoxia-inducible angiogenic factor, overexpression of this mediator, concomitant with hypervascularity, may be induced more strongly in malignant thyroid tumors, which need more oxygen to proliferate, than in benign follicular tumors. However, neither VEGF nor CD34 was expressed in anaplastic thyroid carcinoma, which is an extremely poorly differentiated malignant tumor. CD34 but not VEGF was expressed in the hyperplastic thyroid tissues of Graves’ disease composed of nontransformed cells. Thus, the expression of VEGF concomitant with CD34 is suggested to reflect both the transformation and differentiation state of malignant tumors.

Ferrara N, Henzel WJ (1989) Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858CrossRefPubMed

Rosenthal RA, Megyesi JF, Henzei WJ, Ferrara N, Folkman J (1990) Conditioned medium from mouse sarcoma 180 cells contains vascular endothelial growth factor. Growth Factor 4:53–59CrossRef

Houck KA, Ferrara N, Winer J, Cachianes G, Li B, Leung DW (1991) The vascular endothelial growth factor family: identification of a fourth molecular species and characterization of alternative splicing of RNA. Mol Endocrinol 5:1806–1814CrossRefPubMed

De Vries C, Escobedo JA, Ueno H, Houck K, Ferrara N, Williams LT (1992) The fms-like tyrosine kinase, a receptor for vascular endothelial growth factor. Science 255:989–991CrossRefPubMed

Shibuya M (1995) Role of VEGF-Flt receptor system in normal and tumor angiogenesis. Adv Cancer Res 67:281–316CrossRefPubMed

Peters KG, De Vries C, Williams LT (1993) Vascular endothelial growth factor receptor expression during embryogenesis and tissue repair suggests a role in endothelial differentiation and blood vessel growth. Proc Natl Acad Sci USA 90:8915–8919CrossRefPubMed

Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR, Thieme H, Iwamoto MA, Park JE (1994) Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med 331:1480–1487CrossRefPubMed

Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359:843–845CrossRefPubMed

Brown LF, Berse B, Jackman RW, Tognazzi K, Manseau EJ, Dvorak HF, Senger DR (1993) Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am J Pathol 143:1255–1262PubMed

10.

Plate KH, Breier G, Weich HA, Risau W (1992) Vascular endothelial growth factor is a potential tumour angiogenesis factor in human gliomas in vivo. Nature 359:845–848CrossRefPubMed

11.

Toi M, Hoshina S, Takayanagi T, Tominaga T (1994) Association of vascular endothelial growth factor expression with tumor angiogenesis and with early relapse in primary breast cancer. Jpn J Cancer Res 85:1045–1049PubMed

12.

Kobayashi T, Himeno Y, Hotta K, Nagata M, Itoh A, Nagasaka A, Oda N, Senda T, Itoh M (2005) The expression of vascular endothelial growth factor (VEGF) in thyroid tissues of various thyroid diseases. Bull Fujita Med Soc 29:77–78

13.

de la Torre NG, Buley I, Wass JA, Turner HE (2006) Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour. Endocr Relat Cancer 13:931–944CrossRef

14.

Ramsden D (2000) Angiogenesis in the thyroid gland. J Endocrinol 166:475–480CrossRefPubMed

15.

Tuttle RM, Fleisher M, Francis GL, Robbins RJ (2002) Serum vascular endothelial growth factor levels are elevated in metastatic differentiated thyroid cancer but not increased by short-term TSH stimulation. Clin Endocrinol Metab 87:1737–1742CrossRef

16.

Iitaka M, Miura S, Yamanaka K, Kawasaki S, Kitahama S, Kawakami Y, Kakinuma S, Oosuga I, Wada S, Katayama S (1998) Increased serum vascular endothelial growth factor levels and intrathyroidal vascular area in patients with Graves’ disease and Hashimoto’s thyroiditis. J Clin Endocrinol Metab 83:3908–3912CrossRefPubMed

17.

Fenton C, Patel A, Dinauer C, Robie DK, Tuttle RM, Francis GL (2000) The expression of vascular endothelial growth factor and the type 1 vascular endothelial growth factor receptor correlate with the size of papillary thyroid carcinoma in children and young adults. Thyroid 10:349–357CrossRefPubMed

18.

Wang JF, Milosveski V, Schramek C, Fong GH, Becks GP, Hill DJ (1998) Presence and possible role of vascular endothelial growth factor in thyroid cell growth and function. J Endocrinol 157:5–12CrossRefPubMed

19.

Soh EY, Duh QY, Sobhi SA, Young DM, Epstein HD, Wong MG, Garcia YK, Min YD, Grossman RF, Siperstein AE, Clark OH (1997) Vascular endothelial growth factor expression is higher in differentiated thyroid cancer than in normal or benign thyroid. J Clin Endocrinol Metab 82:3741–3747CrossRefPubMed

20.

Katoh R, Miyagi E, Kawaoi A, Hemmi A, Komiyama A, Oyama T, Shibuya M (1999) Expression of vascular endothelial growth factor (VEGF) in human thyroid neoplasms. Hum Pathol 30:891–897CrossRefPubMed

21.

Lennard CM, Patel A, Wilson J, Reinhardt B, Tuman C, Fenton C, Blair E, Francis GL, Tuttle RM (2001) Intensity of vascular endothelial growth factor expression is associated with increased risk of recurrence and decreased disease-free survival in papillary thyroid cancer. Surgery 129:552–558CrossRefPubMed

22.

Klein M, Picard E, Vignaud JM, Marie B, Bresler L, Toussaint B, Weryha G, Duprez A, Leclere J (1999) Vascular endothelial growth factor gene and protein: strong expression in thyroiditis and thyroid carcinoma. J Endocrinol 161:41–49CrossRefPubMed

23.

Viglietto G, Maglione D, Rambaldi M, Cerutti J, Romano A, Trapasso F, Fedele M, Ippolito P, Chiappetta G, Botti G, Fusco A, Persico G (1995) Upregulation of vascular endothelial growth factor (VEGF) and downregulation of placenta growth factor (PIGF) associated with malignancy in human thyroid tumors and cell lines. Oncogene 11:1569–1579PubMed

24.

Fellmer PT, Sato K, Tanaka R, Okamoto T, Kato Y, Kobayashi M, Shibuya M, Obara T (1999) Vascular endothelial growth factor-C gene expression in papillary and follicular thyroid carcinomas. Surgery 126:1056–1062CrossRefPubMed

25.

Bunone G, Vigneri P, Mariani L, Buto S, Collini P, Pilotti S, Pierotti MA, Bongarzone I (1999) Expression of angiogenesis stimulators and inhibitors in human thyroid tumors and correlation with clinical pathological features. Am J Pathol 155:1967–1976PubMed

26.

Klein M, Vignaud JM, Hennequin V, Toussaint B, Bresler L, Plenat F, Leclere J, Duprez A, Weryha G (2001) Increased expression of the vascular endothelial growth factor is a pejorative prognosis marker in papillary thyroid carcinoma. J Clin Endocrinol Metab 86:656–658CrossRefPubMed

27.

Nagura S, Kato R, Miyagi E, Shibuya M, Kawaoi A (2001) Expression of vascular endothelial growth factor (VEGF) and VEGF receptor-1 (Flt-1) in Graves’ disease possibly correlated with increased vascular density. Hum Pathol 32:10–17CrossRefPubMed

28.

Viglietto G, Romano A, Manzo G, Chiappetta G, Paoletti I, Califano D, Galati MG, Mauriello V, Bruni P, Lago CT, Fusco A, Persico MG (1997) Upregulation of the angiogenic factors P1GF, VEGF and their receptors (Flt-1, Flk-1/KDR) by TSH in cultured thyrocytes and in the thyroid gland of thiouracil-fed rats suggests a TSH-dependent paracrine mechanism for goiter hypervascularization. Oncogene 15:2687–2698CrossRefPubMed

29.

Sato K, Yamazaki K, Shizume K, Kanaji Y, Obara T, Ohsumi K, Demura H, Yamaguchi S, Shibuya M (1995) Stimulation by thyroid-stimulating hormone and Graves’ immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo. J Clin Invest 96:1295–1302CrossRefPubMed

30.

Soh EY, Sobhi SA, Wong MG, Siperstein AE, Clark OH, Duh QY (1996) Thyroid-stimulating hormone promotes the secretion of vascular endothelial growth factor in thyroid cancer cell lines. Surgery 120:944–947CrossRefPubMed

31.

Potey M, Delemer B, Bellon G, Martiny L, Pluot M, Hage B (1999) Immunohistochemical study of thrombospondin and its receptors B3 and CD36 in normal thyroid and in thyroid tumours. J Clin Pathol 52:895–900CrossRef

32.

Kim KJ, Li B, Winer J, Armanini M, Gillett N, Phillips HS, Ferrara N (1993) Inhibition of vascular endothelial growth factor–induced angiogenesis suppresses tumor growth in vivo. Nature 362:841–844CrossRefPubMed

33.

Kebebew E, Wong MG, Siperstein AE, Duh QY, Clark OH (1999) Phenylacetate inhibits growth and vascular endothelial growth factor secretion in human thyroid carcinoma cells and modulates their differentiated function. J Clin Endocrinol Metab 84:2840–2847CrossRefPubMed

34.

Soh EY, Eigelberger MS, Kim KJ, Wong MG, Young DM, Clark OH, Duh QY (2000) Neutralizing vascular endothelial growth factor activity inhibits thyroid cancer growth in vivo. Surgery 128:1059–1066CrossRefPubMed

35.

Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434CrossRefPubMed

Title: Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders
Authors: Asako Itoh
Katsumi Iwase
Shin Jimbo
Haruo Yamamoto
Naoki Yamamoto
Masahiro Kokubo
Takao Senda
Akira Nakai
Akio Nagagasaka
Takaaki Nagasaka
Yatsuka Hibi
Teppei Seko
Publication date: 01-02-2010
Publisher: Springer-Verlag
Published in: World Journal of Surgery / Issue 2/2010
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI: https://doi.org/10.1007/s00268-009-0344-4

At a glance: The STEP trials

Springer Medicine

Expression of Vascular Endothelial Growth Factor and Presence of Angiovascular Cells in Tissues from Different Thyroid Disorders

Abstract

Background

Materials and methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Materials and methods

Results

Conclusions

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