Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression.
Microvascular density and hypoxia-inducible factor pathway in pancreatic endocrine tumours: negative correlation of microvascular density and VEGF expression with tumour progression.
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DOI：
10.1038/sj.bjc.6602245
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发表时间：
2005-01-17
影响因子：
8.8
通讯作者：
Pezzella, F
中科院分区：
文献类型：
--
作者：
Couvelard, A;O'Toole, D;Turley, H;Leek, R;Sauvanet, A;Degott, C;Ruszniewski, P;Belghiti, J;Harris, AL;Gatter, K;Pezzella, F
肿瘤相关血管生成受缺氧诱导因子（HIF）途径的部分调控。内分泌肿瘤是高度血管化的，其血管生成的分子机制尚不完全清楚。本研究的目的是评估血管生成和hif相关分子在一系列胰腺内分泌肿瘤（pet）患者中的表达。采用免疫组化方法检测45例pet患者血管内皮生长因子（VEGF）、HIF-1α、HIF-2α和碳酸酐酶9 （CA9）的表达，并与微血管密度（MVD）、内皮细胞增殖、肿瘤分期及生存期进行比较。pet微血管密度非常高，与内皮细胞增殖指数低有关。良性pet的微血管密度明显高于预后不确定、高分化癌和低分化癌的pet（平均值分别为535、436、252和45支血管mm−2，P<0.0001）。分化良好的肿瘤细胞质中VEGF和HIF-1α的表达较高。低分化癌与核HIF-1α和膜CA9表达相关。低MVD （P=0.0001）和膜CA9表达（P=0.0004）与较差的生存率相关。与其他类型的癌症相反，pet是高度血管化的，但血管生成性差的肿瘤。随着病程的发展，VEGF表达减少，MVD显著降低。HIF信号的调控似乎在胰腺内分泌肿瘤中具有特异性。
Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series of patients with pancreatic endocrine tumours (PETs). The expression of vascular endothelial growth factor (VEGF), HIF-1α, HIF-2α and carbonic anhydrase 9 (CA9) was examined by immunohistochemistry in 45 patients with PETs and compared to microvascular density (MVD), endothelial proliferation, tumour stage and survival. Microvascular density was very high in PETs and associated with a low endothelial index of proliferation. Microvascular density was significantly higher in benign PETs than in PETs of uncertain prognosis, well-differentiated and poorly differentiated carcinomas (mean values: 535, 436, 252 and 45 vessels mm−2, respectively, P<0.0001). Well-differentiated tumours had high cytoplasmic VEGF and HIF-1α expression. Poorly differentiated carcinomas were associated with nuclear HIF-1α and membranous CA9 expression. Low MVD (P=0.0001) and membranous CA9 expression (P=0.0004) were associated with a poorer survival. Contrary to other types of cancer, PETs are highly vascularised, but poorly angiogenic tumours. As they progress, VEGF expression is lost and MVD significantly decreases. The regulation of HIF signalling appears to be specific in pancreatic endocrine tumours.
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影响因子：
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通讯作者：
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通讯作者：
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