Lymphangiogenesis and angiogenesis in bladder cancer: Prognostic implications and regulation by vascular endothelial growth factors-A, -C, and -D
Lymphangiogenesis and angiogenesis in bladder cancer: Prognostic implications and regulation by vascular endothelial growth factors-A, -C, and -D
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DOI：
10.1158/1078-0432.ccr-05-1284
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发表时间：
2006-02-01
影响因子：
11.5
通讯作者：
Kanetake, H
中科院分区：
文献类型：
--
作者：
Miyata, Y;Kanda, S;Kanetake, H
目的：淋巴管密度（LVD）和微血管密度（MVD）与肿瘤的恶性潜能和患者生存率相关。血管内皮生长因子（VEGF）-A、VEGF-C和VEGF-D可调节LVD和MVD。我们研究了LVD和MVD对VEGF-A，VEGF-C和VEGF-D在人膀胱cancer.Experimental Designs中淋巴管生成和血管生成功能的临床和预后意义：我们回顾了来自非转移性膀胱癌患者的组织样本，这些患者接受了经尿道切除术（n = 126）。应用计算机图像分析系统测量D2-40阳性血管（LVD）和CD 34阳性血管（MVD）的密度。VEGF-A，VEGF-C和VEGF-D的表达进行了检查，免疫组化;生存分析和他们的独立角色进行了研究，使用多变量分析models.Results：LVD与肿瘤分级，但不与pT阶段。LVD与无转移生存率相关（对数秩P = 0.039），但不是独立的预后因素。虽然MVD影响生存率，但肿瘤中高LVD和高MVD的组合是无转移生存率的独立预测因素。VEGF-C表达与LVD和MVD均呈正相关，VEGF-D仅与LVD相关，VEGF-A表达与MVD相关，但不是独立因素。结论：淋巴管生成和血管生成影响无转移生存率，并受VEGF-C和/或VEGF-D的调节。我们的研究结果表明，LVD和MVD是膀胱癌患者术后管理和治疗策略选择的有用工具。
Purpose: Lymph vessel density (LVD) and microvessel density (MVD) correlate with the malignant potential of tumors and patient survival. Vascular endothelial growth factors (VEGF) -A, VEGF-C, and VEGF-D could modulate LVD and MVD. We investigated the clinical and prognostic significance of LVD and MVD on lymphangiogenic and angiogenic function of VEGF-A,VEGF-C, and VEGF-D in human bladder cancer.Experimental Design: We reviewed tissue samples from patients with nonmetastatic bladder cancer who had undergone transurethral resections (n = 126). The densities of D2-40-positive vessels (LVD) and CD34-positive vessels (MVD) were measured by a computer-aided image analysis system. Expression of VEGF-A, VEGF-C, and VEGF-D was examined by immunohistochemistry; survival analyses and their independent roles were investigated using multivariate analysis models.Results: LVD was associated with tumor grade but not with pT stage. LVD was associated with metastasis-free survival (log rank P = 0.039), but was not an independent prognostic factor. Although MVD affected survival, the combination of high LVD and high MVD in tumors was an independent predictor of metastasis-free survival. Although VEGF-C expression was positively associated with both LVD and MVD,VEGF-D was associated only with LVD.VEGF-A expression was associated with MVD in univariate analysis, however, it was not an independent factor.Conclusions: Lymphangiogenesis and angiogenesis influence metastasis-free survival, and are regulated by VEGF-C and/or VEGF-D. Our results suggest that LVD and MVD are useful tools for the selection of postoperative management and treatment strategies in patients with bladder cancer.