title: Inhibition of infiltration and angiogenesis by thrombospondin-1 in papillary thyroid carcinoma.
abstract: OBJECTIVE
  Angiogenesis is essential for tumor growth and is controlled by the balance between angiogenic and antiangiogenic factors. We studied the expression of angiogenic factors and antiangiogenic factors in papillary thyroid carcinoma.
  
  
  METHODS
  We investigated immunohistochemically the expression patterns and levels of antiangiogenic factor and its receptor, thrombospondin-1 (TSP-1) and CD36, and four angiogenic factors, vascular endothelial growth factor (VEGF), VEGF-C, angiopoietin-2 (Ang-2), and Tie-2, in the primary tumors of 75 papillary thyroid carcinoma patients. We also examined the microvessel count (MVC), using CD31 staining.
  
  
  RESULTS
  VEGF expression strongly correlated with other angiogenic factors. The cytoplasm of cancer cells stained positive for all factors. Tie-2 and TSP-1 receptor also appeared in endothelia of microvessels. TSP-1 inversely correlated with the degree of invasion of the primary tumor to other adjacent organs and with MVC. A higher MVC correlated with poorer survival. To clarify the balance between angiogenic and antiangiogenic factors in the same tumor, we calculated the ratio of each angiogenic factor against TSP-1 as the antiangiogenic factor. The ratios VEGF/TSP-1, VEGF-C/TSP-1, and Ang-2/TSP-1 significantly correlated with a higher MVC. Furthermore, the ratios VEGF/TSP-1 and Ang-2/TSP-1 significantly correlated with the degree of infiltration.
  
  
  CONCLUSIONS
  To the best of our knowledge, this is the first report demonstrating that the balance between angiogenic and antiangiogenic factors correlates with distinct invasion to other organs and neovascularization of papillary thyroid carcinoma.
authors: The Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki 701-0192, Japan. tanakaka@med.kawasaki-m.ac.jp
authors: Katsuhiro
authors: K
authors: Tanaka
authors: Hiroshi
authors: H
authors: Sonoo
authors: Junichi
authors: J
authors: Kurebayashi
authors: Tsunehisa
authors: T
authors: Nomura
authors: Sumiko
authors: S
authors: Ohkubo
authors: Yutaka
authors: Y
authors: Yamamoto
authors: Shigeru
authors: S
authors: Yamamoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D042702:Angiopoietin-2; D018955:CD36 Antigens / Q000032:analysis; D002291:Carcinoma, Papillary / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D016228:Endothelial Growth Factors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D011506:Proteins / Q000032:analysis; D011518:Proto-Oncogene Proteins; D042787:Receptor, TIE-2; D019700:Thrombospondin 1 / Q000096:biosynthesis / Q000502:physiology*; D013964:Thyroid Neoplasms / Q000098:blood supply / Q000378:metabolism / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042442:Vascular Endothelial Growth Factors
chemical_list: D042702:Angiopoietin-2; D018955:CD36 Antigens; D016228:Endothelial Growth Factors; D008222:Lymphokines; C105373:MEN1 protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042442:Vascular Endothelial Growth Factors; D042787:Receptor, TIE-2