Gaumann Andreas, Strubel Gerson, Bode-Lesniewska Beata, Schmidtmann Irene, Kriegsmann Jörg, Kirkpatrick C James
Institut für Pathologie, Klinikum der Universität Regensburg, D-93053 Regensburg, Germany.
Oncol Rep. 2008 Aug;20(2):309-18.
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.
新生血管生成参与恶性肿瘤的发生和发展。血管内皮生长因子（VEGF）及其受体在这一过程中起核心作用。由于软组织肿瘤中血管生成评估的意义仍存在争议，我们研究了心脏黏液瘤的血管化情况，并将其与肺动脉肉瘤（PAS）进行比较。通过形态计量学评估了18例PAS和20例黏液瘤中的血管生成。对生长因子及其受体、缺氧诱导因子-1α（HIF-1α）和肿瘤相关巨噬细胞（TAM）进行了免疫组化分析。结果显示，PAS中坏死边缘的微血管密度（MVD）显著高于无坏死区域，但PAS与黏液瘤之间未观察到差异。与黏液瘤相比，坏死边缘的血管表面积（VSA）和血管间距离显示出更高的血管化程度，但不显著。PAS中的VEGF表达高于黏液瘤，且在坏死部位突出。PAS中坏死边缘HIF-1α表达明显，但黏液瘤中无表达。黏液瘤中巨噬细胞浸润明显高于肉瘤。VEGFR-2表达主要在肿瘤外周的肿瘤细胞亚群和血管中检测到，而VEGFR-1在肿瘤中弱表达，但在心脏黏液瘤的巨噬细胞中突出。血小板衍生生长因子受体及其配体在黏液瘤中大量存在，在肉瘤中含量较少。总之，具有不同病理生理学的良性和恶性心血管肿瘤具有相似的血管化程度。缺氧似乎是肉瘤中新生血管生成的最强诱导因素。VEGF家族受体酪氨酸激酶的表达为辅助治疗提供了依据。
