The role of tumor vascularisation in benign and malignant cardiovascular neoplasms: a comparison of cardiac myxoma and sarcomas of the pulmonary artery.
Neoangiogenesis is involved in the development and progression of malignant tumors. Vascular endothelial growth factor (VEGF) and its receptors have been designated a central part in this process. Since the significance of the assessment of angiogenesis in soft tissue tumors is still a matter of debate, we investigated the vascularisation of cardiac myxomas and compared it with pulmonary artery sarcomas (PAS). Angiogenesis in 18 PAS and 20 myxomas was assessed by morphometry. An immunohistochemical analysis of growth factors and their receptors, HIF-1alpha and tumor-associated macrophages (TAM) was performed. Results showed that microvessel density (MVD) in PAS was significantly higher at the border of necrosis versus the areas without necrosis but no difference was observed between PAS and myxomas. Vascular surface area (VSA) and intervascular distances showed a higher vascularisation at the border of necrosis compared to myxomas, which was not significant. VEGF expression was higher in PAS compared to myxomas and was prominent at the sites of necrosis. HIF-1alpha expression was marked at the border of necrosis in PAS but was absent in myxomas. Infiltration of the macrophages was significantly higher in myxomas compared to the sarcomas. VEGFR-2 expression was detected in a subset of tumor cells and in blood vessels mainly at the tumor periphery, whereas VEGFR-1 was weakly expressed in the tumors but prominent in the macrophages in cardiac myxomas. PDGF receptors and their ligands are strongly present in myxomas and to a lesser extent in the sarcomas. In conclusion, benign and malignant cardiovascular tumors with a different pathophysiology develop a comparable vascularisation. Hypoxia appears to be the strongest inducer of neoangiogenesis in the sarcomas. The expression of receptor tyrosine kinases of the VEGF family provides a basis for an adjuvant therapy.
Gaumann
Andreas
A
Institut für Pathologie, Klinikum der Universität Regensburg, D-93053 Regensburg, Germany. andreas.gaumann@klinik.uni-regensburg.de
Strubel
Gerson
G
Bode-Lesniewska
Beata
B
Schmidtmann
Irene
I
Kriegsmann
Jörg
J
Kirkpatrick
C James
CJ
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D005260:Female; D006338:Heart Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009232:Myxoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D011651:Pulmonary Artery; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000378:metabolism; D012509:Sarcoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D019043:Vascular Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D020796:Receptor, Platelet-Derived Growth Factor alpha; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D000469:Alkaline Phosphatase