Sipos Bence, Klapper Wolfram, Kruse Marie-Luise, Kalthoff Holger, Kerjaschki Dontscho, Klöppel Günter
Department of Pathology, University of Kiel, Michaelisstr. 11, 24105 Kiel, Germany.
Am J Pathol. 2004 Oct;165(4):1187-97. doi: 10.1016/S0002-9440(10)63379-2.
Lymphangiogenesis is thought to promote the progression of malignant tumors. Because the lymphangiogenic factors vascular endothelial factor (VEGF)-C and -D are expressed in endocrine cells, we investigated their expression in pancreatic endocrine tumors (PETs) and correlated these data and intratumoral lymph vessel density (iLVD) with clinicopathological features. Lymph vessels were identified with anti-podoplanin antiserum and with podoplanin/proliferating cell nuclear antigen double labeling. PETs (n = 104) were investigated by immunohistochemical staining for VEGF, basic fibroblast growth factor, and VEGF-C expression. VEGF-C and VEGF-D mRNA were quantified by real-time reverse transcriptase-polymerase chain reaction. PETs showed higher iLVD than normal pancreata, but iLVD did not discriminate between benign and malignant PETs. In PETs proliferating lymph vessels were identified. High iLVD was associated with lymph vessel invasion and it was more frequent in angioinvasive/metastatic tumors than in grossly invasive tumors. VEGF-C expression correlated with iLVD as well as with glucagon and pancreatic polypeptide expression. PETs show intratumoral lymphangiogenesis, which is associated with VEGF-C expression in tumor cells. The association between iLVD and lymph vessel invasion and angioinvasive/metastatic features in PETs suggests that lymphangiogenesis may promote malignant progression of PETs. PET is the first human tumor entity in which VEGF-C-related intratumoral lymphangiogenesis has been demonstrated.
淋巴管生成被认为会促进恶性肿瘤的进展。由于淋巴管生成因子血管内皮生长因子（VEGF）-C和-D在内分泌细胞中表达，我们研究了它们在胰腺内分泌肿瘤（PETs）中的表达，并将这些数据以及肿瘤内淋巴管密度（iLVD）与临床病理特征进行关联。通过抗血小板内皮细胞黏附分子抗血清以及血小板内皮细胞黏附分子/增殖细胞核抗原双重标记来识别淋巴管。通过免疫组织化学染色研究104例PETs中VEGF、碱性成纤维细胞生长因子和VEGF-C的表达。通过实时逆转录聚合酶链反应对VEGF-C和VEGF-D mRNA进行定量。PETs的iLVD高于正常胰腺，但iLVD无法区分良性和恶性PETs。在PETs中识别出增殖的淋巴管。高iLVD与淋巴管侵犯相关，在血管侵袭性/转移性肿瘤中比在大体侵袭性肿瘤中更常见。VEGF-C的表达与iLVD以及胰高血糖素和胰多肽的表达相关。PETs显示肿瘤内淋巴管生成，这与肿瘤细胞中VEGF-C的表达相关。PETs中iLVD与淋巴管侵犯以及血管侵袭性/转移性特征之间的关联表明，淋巴管生成可能促进PETs的恶性进展。PET是首个被证实存在与VEGF-C相关的肿瘤内淋巴管生成的人类肿瘤实体。
