淋巴管密度与血管内皮生长因子 A（VEGF-A）表达与胰腺腺癌临床病理特征和生存的关系。
The relationship between lymphatic vascular density and vascular endothelial growth factor A (VEGF-A) expression with clinical-pathological features and survival in pancreatic adenocarcinomas.
机构信息
Departament of Pathology, Ribeirão Preto Medical School, University of São Paulo, 3900 Bandeirantes Avenue, Ribeirão Preto, São Paulo, Brazil.
出版信息
Diagn Pathol. 2013 Oct 18;8:170. doi: 10.1186/1746-1596-8-170.
BACKGROUND
Pancreatic cancer is a rare tumor with an extremely low survival rate. Its known risk factors include the chronic use of tobacco and excessive alcohol consumption and the presence of chronic inflammatory diseases, such as pancreatitis and type 2 diabetes. Angiogenesis and lymphangiogenesis, which have been the focus of recent research, are considered prognostic factors for cancer development. Knowing the angiogenic and lymphangiogenic profiles of a tumor may provide new insights for designing treatments according to the different properties of the tumor. The aim of this study was to evaluate the density of blood and lymphatic vessels, and the expression of VEGF-A, in pancreatic adenocarcinomas, as well as the relationship between blood and lymphatic vascular density and the prognostically important clinical-pathological features of pancreatic tumors.
METHODS
Paraffin blocks containing tumor samples from 100 patients who were diagnosed with pancreatic cancer between 1990 and 2010 were used to construct a tissue microarray. VEGF expression was assessed in these samples by immunohistochemistry. To assess the lymphatic and vascular properties of the tumors, 63 cases that contained sufficient material were sectioned routinely. The sections were then stained with the D2-40 antibody to identify the lymphatic vessels and with a CD34 antibody to identify the blood vessels. The vessels were counted individually with the Leica Application Suite v4 program. All statistical analyses were performed using SPSS 18.0 (Chicago, IL, USA) software, and p values ≤ 0.05 were considered significant.
RESULTS
In the Cox regression analysis, advanced age (p=0.03) and a history of type 2 diabetes (p=0.014) or chronic pancreatitis (p=0.02) were shown to be prognostic factors for pancreatic cancer. Blood vessel density (BVD) had no relationship with clinical-pathological features or death. Lymphatic vessel density (LVD) was inversely correlated with death (p=0.002), and by Kaplan-Meyer survival analysis, we found a significant association between low LVD (p=0.021), VEGF expression (p=0.023) and low patient survival.
CONCLUSIONS
Pancreatic carcinogenesis is related to a history of chronic inflammatory processes, such as type 2 diabetes and chronic pancreatitis. In pancreatic cancer development, lymphangiogenesis can be considered an early event that enables the dissemination of metastases. VEGF expression and low LVD can be considered as poor prognostic factors as tumors with this profile are fast growing and highly aggressive.
VIRTUAL SLIDES
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5113892881028514.
背景
胰腺癌是一种罕见的肿瘤，其存活率极低。其已知的风险因素包括长期使用烟草和过量饮酒以及慢性炎症性疾病，如胰腺炎和 2 型糖尿病。血管生成和淋巴管生成是最近研究的焦点，被认为是癌症发展的预后因素。了解肿瘤的血管生成和淋巴管生成特征可能为根据肿瘤的不同特性设计治疗方法提供新的见解。本研究旨在评估胰腺腺癌的血管和淋巴管密度，以及 VEGF-A 的表达，并探讨血管和淋巴管密度与胰腺肿瘤预后重要的临床病理特征之间的关系。
方法
使用包含 1990 年至 2010 年间诊断为胰腺癌的 100 名患者肿瘤样本的石蜡块构建组织微阵列。通过免疫组织化学评估这些样本中的 VEGF 表达。为了评估肿瘤的淋巴和血管特性，对 63 例含有足够材料的病例进行常规切片。然后用 D2-40 抗体识别淋巴管，用 CD34 抗体识别血管。使用 Leica Application Suite v4 程序单独对血管进行计数。所有统计分析均使用 SPSS 18.0（芝加哥，IL，美国）软件进行，p 值≤0.05 被认为具有统计学意义。
结果
在 Cox 回归分析中，年龄较大（p=0.03）和 2 型糖尿病史（p=0.014）或慢性胰腺炎史（p=0.02）被证明是胰腺癌的预后因素。血管密度（BVD）与临床病理特征或死亡无关。淋巴管密度（LVD）与死亡呈负相关（p=0.002），通过 Kaplan-Meier 生存分析发现，LVD 低（p=0.021）、VEGF 表达（p=0.023）与患者低生存率之间存在显著关联。
结论
胰腺癌变与慢性炎症过程有关，如 2 型糖尿病和慢性胰腺炎。在胰腺癌的发展过程中，淋巴管生成可以被认为是转移扩散的早期事件。VEGF 表达和低 LVD 可被视为不良预后因素，因为具有这种特征的肿瘤生长迅速且侵袭性强。
虚拟幻灯片
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