High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas
High expression of vascular endothelial growth factor predicts early recurrence and poor prognosis after curative resection for ductal adenocarcinoma of the pancreas
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DOI：
10.1097/00006676-200208000-00002
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发表时间：
2002-08-01
期刊：
影响因子：
2.9
通讯作者：
Post, S
中科院分区：
文献类型：
--
作者：
Niedergethmann, M;Hildenbrand, R;Post, S
介绍和目标：胰腺癌只有根治性切除才能获得良好的预后，但术后总体生存率仍然很低，并且经常观察到早期复发。由于复发是限制因素和治愈性切除术后死亡的主要原因，识别预测早期术后复发的标志物是至关重要的。血管生成对于肿瘤生长和转移是必不可少的;因此，我们着手阐明血管内皮生长因子（VEGF）表达和微血管密度（MVD）是否与根治性切除术后的早期复发和预后不良相关。第二个目标是表征产生VEGF的细胞和亚细胞分布。方法：70例胰腺导管腺癌患者在根治性切除后进行了至少2年的随访研究。使用抗CD 34单克隆抗体进行免疫化学法MVD定量。用多克隆抗体检测VEGF的表达。为了检测特异性VEGF mRNA序列的细胞内定位，进行了非同位素原位杂交。分析VEGF表达与MVD、临床病理参数及临床预后的关系。结果：VEGF免疫反应阳性率为88.6%，81.4%的癌组织和内皮细胞胞浆中表达阳性。此外，我们观察到肿瘤相关巨噬细胞靠近浸润的癌细胞。所有内皮细胞均显示抗CD 34抗体阳性免疫反应性，观察到中位分布为85条血管/x200视野。MVD与国际抗癌联合会（UICC）分期显著相关（P < 0.05）。统计学分析显示VEGF表达与MVD高度相关（p < 0.05）。Kaplan-Meier分析显示VEGF表达和MVD与根治性切除术后生存率有显著相关性（p < 0.05）。此外，多变量分析表明，VEGF表达是根治性手术后8个月内癌症复发的独立预后标志物（p = 0.003）。结论：在胰腺癌中，VEGF的表达和MVD的高度密切相关，两者-而不是UICC分期和TNM分类（肿瘤大小和淋巴结受累）-是根治性切除术后预后相关性的标志物。此外，VEGF是根治性切除术后早期复发的预测因子。目前的研究表明，VEGF可能会促进转移的分布，导致早期癌症复发和预后不良。
Introduction and Aims: Only curative resection for pancreatic adenocarcinoma is related to a favorable prognosis, but the overall survival after surgery still remains poor, and early recurrence is frequently observed. Because recurrence is the limiting factor and the main cause of death after curative resection, the identification of markers that predict early postoperative recurrence is of paramount importance. Angiogenesis is essential for tumor growth and metastases; therefore, we set out to clarify whether vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) correlate with early recurrence and poor prognosis after curative resection. A second goal was to characterize the VEGF-producing cells and the subcellular distribution. Methodology: Seventy patients with ductal adenocarcinoma of the pancreas were studied after curative resection with a follow-up of at least 2 years. The MVD quantification was performed immunohistochemically with use of a monoclonal antibody to CD34. The VEGF expression was studied with use of polyclonal antibody. To detect the intracellular localization of specific VEGF mRNA sequences, nonisotopic in situ hybridization was performed. The correlations among VEGF expression and MVD, clinicopathologic parameters, and clinical outcome were then statistically analyzed. Results: The VEGF immunoreactivity was 88.6%, and positive mRNA signals were obtained in the cytoplasm of carcinoma and endothelial cells in 81.4%. Furthermore, we observed tumor-associated macrophages close to infiltrating carcinoma cells. All endothelial cells showed positive immunoreactivity to the anti-CD34 antibody, and a median distribution of 85 vessels/x200 field was observed. A significant correlation (p < 0.05) was found between the MVD and the International Union Against Cancer (UICC) stage. Statistical analysis showed a significant correlation between VEGF expression and the height of MVD (p < 0.05). Kaplan-Meier analyses revealed that VEGF expression and MVD had a statistically significant correlation with survival after curative resection (p < 0.05). Furthermore, multivariate analysis indicated that VEGF expression is an independent prognostic marker for cancer recurrence within 8 months after curative surgery (p = 0.003). Conclusion: In pancreatic adenocarcinoma, the VEGF expression and the height of MVD are closely correlated, and both-rather than UICC stage and TNM classification (tumor size and nodal involvement)-are markers of prognostic relevance after curative resection. Furthermore, VEGF is a predictor of early recurrence after curative resection. The current study indicates that VEGF may promote the distribution of metastases, leading to early cancer recurrence and poor outcome.