Bierer S, Herrmann E, Köpke T, Neumann J, Eltze E, Hertle L, Wülfing C
Department of Urology, University Hospital Münster, Münster, Germany.
Oncol Rep. 2008 Oct;20(4):721-5.
The vascular endothelial growth factors VEGF-C, VEGF-D and its receptor, VEGFR-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. We analysed these factors in clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma (RCC). The results were correlated with various clinicopathological parameters (CPP). We constructed a tissue microarray with tumor samples of 135 (81%) ccRCC and 31 (19%) pRCC. After immunohistochemical staining using polyclonal antibodies for VEGF-C, VEGF-D and VEGFR-3, a semiquantitative analysis was performed to determine the levels of expression. The results were compared between the two subgroups and were correlated with CPP. In the two subgroups the expression of VEGF-C was significantly correlated with that of VEGF-D (p<0.001). There was an increased expression of VEGF-C in 11% of ccRCC and 36% of pRCC (p=0.002). VEGF-D expression was positive by means of analysis in 22% of ccRCC and 42% of pRCC (p=0.039). There was no significant difference regarding the expression of VEGFR-3 between the subgroups (44% ccRCC and 61% pRCC, p=0.11). No correlation was found between the expression of the analysed parameters and CPP (TNM, grading, progression-free survival and overall survival) in either the entire group or in the two subgroups. In summary, ccRCC and pRCC show a different expression pattern of the analysed lymphangiogenic factors. Further studies are necessary to confirm these results and to determine whether the VEGF-C/VEGF-D/VEGFR-3-axis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma.
血管内皮生长因子VEGF - C、VEGF - D及其受体VEGFR - 3在不同恶性肿瘤中过度表达，与淋巴结转移及预后不良相关。我们分析了透明细胞肾细胞癌（ccRCC）和乳头状肾细胞癌（pRCC）中的这些因子。结果与各种临床病理参数（CPP）相关。我们构建了一个组织芯片，其中包含135例（81%）ccRCC和31例（19%）pRCC的肿瘤样本。使用针对VEGF - C、VEGF - D和VEGFR - 3的多克隆抗体进行免疫组化染色后，进行半定量分析以确定表达水平。比较了两个亚组的结果并与CPP相关联。在两个亚组中，VEGF - C的表达与VEGF - D的表达显著相关（p<0.001）。11%的ccRCC和36%的pRCC中VEGF - C表达增加（p = 0.002）。通过分析，22%的ccRCC和42%的pRCC中VEGF - D表达呈阳性（p = 0.039）。亚组之间VEGFR - 3的表达无显著差异（44%的ccRCC和61%的pRCC，p = 0.11）。在整个组或两个亚组中，所分析参数的表达与CPP（TNM、分级、无进展生存期和总生存期）之间均未发现相关性。总之，ccRCC和pRCC显示出所分析的淋巴管生成因子的不同表达模式。需要进一步研究以证实这些结果，并确定VEGF - C/VEGF - D/VEGFR - 3轴是否可作为肾细胞癌的预后工具或治疗干预靶点发挥作用。
