Increased Percentage of Microvessels but Decreased Density of Large Vessels in Papillary Carcinomas as Compared to Hot and Cold Thyroid Nodules

Abstract

Objective: For thyroid tumors increased as well as decreased vessel densities have been reported. Because of different morphometric methods and specificities of previously used antibodies for small and large vessels our objective was to investigate and compare the density of large vessels and microvessels by different morphometric methods and antibodies in hot nodules(HN), cold nodules (CN), papillary carcinoma (PC) and Graves’ disease (GD) to try to clarify some of these discrepancies.

Design: Tissue sections from 29 HN, 22 CN, 19 PC and 8 GD thyroids were stained with the antibodies for CD34 and alpha-SMA. A computerized image analysis was used to calculate the mean area of endothelium (mEA) and the mean endothelium to tumor epithelial nucleus area ratio (mE/N) in four hot spots and ten systematically selected fields.

Main outcome: We found a consistent increase of the CD34 stained percentage of microvessels in PC as compared to HN and CN determined by the hot spot analysis and systematic field analysis. This increased microvessel density in PC is of a similar magnitude as in GD, which is characterised by a prominent increase of vascularisation during its active disease stage. Our SMA staining results reveal a kind of mirror image of the CD34 staining results with higher vessel counts in the normal surrounding tissues as compared to HN, CN and PC.

Conclusions: The specific immunohistologic detection of microvessels with the CD34 antibody combined with their specific evaluation is able to clearly differentiate PCs from normal tissue, HN and CN.

Key words

multiple endocrine neoplasia - cancer - thyroid - autoimmunity - Graves’ disease

References

• 1 Akslen LA, Livolsi VA. Increased angiogenesis in papillary thyroid carcinoma but lack of prognostic importance.  Hum Pathol. 2000;  31 439-442
• 2 Banner BF, Whitehouse R, Baker SP. et al . Tumor angiogenesis in stage II colorectal carcinoma: association with survival.  Am J Clin Pathol. 1998;  109 733-737
• 3 Benjamin LE, Golijanin D, Itin A. et al . ESelective ablation of immature blood vessels in established human tumors follows vascular endothelial growth factor withdrawal.  J Clin Invest. 1999;  103 159-165
• 4 Cantu De León D, Frias Mendivil M, Chanona Vilchis G, Gomez C, De La Garza Salazar J. Significance of microvascular density (MVD) in cervical cancer recurrence.  Int J Gynecol Cancer. 2003;  13 856-862
• 5 Chan JKC, Hirokawa M, Evans H. et al .Tumours of the Thyroid and Parathyroid: Follicular adenoma. In: DeLellis RA, Lloyd RV, Heitz PU, Eng C, editors. WHO Classification of Tumours: Pathology & Genetics of Tumours of Endocrine Organs. Lyon: IARCPress 2004: 98-103
• 6 Torre NG de la, Buley I, Wass JA. et al . Angiogenesis and lymphangiogenesis in thyroid proliferative lesions: relationship to type and tumour behaviour.  Endocr Relat Cancer. 2006;  13 931-944
• 7 Dhar DK, Kubota H, Kotoh T. et al . Tum, or vascularity predicts recurrence in differentiated thyroid carcinoma.  Am J Surg. 1998;  176 442-447
• 8 Fontanini G, Vignati S, Pacini F. et al . Mic, rovessel count: an indicator of poor outcome in medullary thyroid carcinoma but not in other types of thyroid carcinoma.  Mod Pathol. 1996;  9 636-641
• 9 Fox SB. Quantitative angiogenesis in breast cancer.  Methods Mol Med. 2006;  120 161-187
• 10 Fox SB, Generali DG, Harris AL. Breast tumour angiogenesis.  Breast Cancer Res. 2007;  9 216-21
• 11 Giorgadze TA, Baloch ZW, Pasha T. et al . Lymphatic and blood vessel density in the follicular patterned lesions of thyroid.  Mod Pathol. 2005;  18 1424-1431
• 12 Goldenberg JD, Portugal LG, Wenig BL. et al . Well-differentiated thyroid carcinomas: p53 mutation status and microvessel density.  Head Neck. 1998;  20 152-158
• 13 Herrmann G, Schumm-Draeger PM, Muller C. et al . T lymphocytes, CD68-positive cells and vascularisation in thyroid carcinomas.  J Cancer Res Clin Oncol. 1994;  120 651-656
• 14 Martin L, Green B, Renshaw C. et al . Examining the technique of angiogenesis assessment in invasive breast cancer.  Br J Cancer. 1997;  76 1046-1054
• 15 Parums DV, Cordell JL, Micklem K. et al . JC70: a new monoclonal antibody that detects vascular endothelium associated antigen on routinely processed tissue sections.  J Clin Pathol. 1990;  43 752-757
• 16 Pusztaszeri MP, Seelentag W, Bosman FT. Immunohistochemical expression of endothelial markers CD31, CD34, von Willebrand factor, and Fli-1 in normal human tissues.  J Histochem Cytochem. 2006;  54 385-395
• 17 Sasano H, Suzuki T. Pathological evaluation of angiogenesis in human tumor.  Biomed Pharmacother. 2005;  59 ((Suppl. 2)) S334-S336
• 18 Segal K, Shpitzer T, Feinmesser M. et al . Angiogenesis in follicular tumors of the thyroid.  J Surg Oncol. 1996;  63 95-98
• 19 Stabenow E, Tavares MR, Ab’Saber AM. et al . Angiogenesis as an indicator of metastatic potential in papillary thyroid carcinoma.  Clinics. 2005;  60 233-240
• 20 Turner HE, Harris AL, Melmed S. et al . Angiogenesis in endocrine tumors.  Endocr Rev. 2003;  24 600-632
• 21 Turner HE, Nagy Z, Gatter KC. et al . Angiogenesis in pituitary adenomas and the normal pituitary gland.  J Clin Endocrinol Metab. 2000;  85 1159-1162
• 22 Vermeulen PB, Gasparini G, Fox SB. et al . Quantification of angiogenesis in solid human tumours: an international consensus on the methodology and criteria of evaluation.  Eur J Cancer. 1996;  32A 2474-2484
• 23 Viacava P, Bocci G, Tonacchera M. et al . Markers of cell proliferation, apoptosis, and angiogenesis in thyroid adenomas: a comparative immunohistochemical and genetic investigation of functioning and nonfunctioning nodules.  Thyroid. 2007;  17 191-197
• 24 Vieira SC, Zeferino LC, Da Silva BB. et al . Quantification of angiogenesis in cervical cancer: a comparison among three endothelial cell markers.  Gynecol Oncol. 2004;  93 121-124
• 25 Weidner N, Folkman J, Pozza F. et al . Tumor angiogenesis: a new significant and independent prognostic indicator in early-stage breast carcinoma.  J Natl Cancer Inst. 1992;  84 1875-1887
• 26 Wong NA, Willott J, Kendall MJ. et al . Measurement of vascularity as a diagnostic and prognostic tool for well differentiated thyroid tumours: comparison of different methods of assessing vascularity.  J Clin Pathol. 1999;  52 593-597

1 these authors contributed equally to this study

Correspondence