Inhibition of infiltration and angiogenesis by thrombospondin-1 in papillary thyroid carcinoma.
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.
Tanaka
Katsuhiro
K
The Department of Breast and Thyroid Surgery, Kawasaki Medical School, Kurashiki 701-0192, Japan. tanakaka@med.kawasaki-m.ac.jp
Sonoo
Hiroshi
H
Kurebayashi
Junichi
J
Nomura
Tsunehisa
T
Ohkubo
Sumiko
S
Yamamoto
Yutaka
Y
Yamamoto
Shigeru
S
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
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