Miyata Yasuyoshi, Kanda Shigeru, Ohba Kojiro, Nomata Koichiro, Hayashida Yasushi, Eguchi Jiro, Hayashi Tomayoshi, Kanetake Hiroshi
Department of Urology, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan.
Clin Cancer Res. 2006 Feb 1;12(3 Pt 1):800-6. doi: 10.1158/1078-0432.CCR-05-1284.
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.
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.
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.
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.
淋巴管密度（LVD）和微血管密度（MVD）与肿瘤的恶性潜能及患者生存率相关。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对人膀胱癌中VEGF-A、VEGF-C和VEGF-D淋巴管生成和血管生成功能的临床及预后意义。
我们回顾了126例接受经尿道切除术的非转移性膀胱癌患者的组织样本。通过计算机辅助图像分析系统测量D2-40阳性血管的密度（LVD）和CD34阳性血管的密度（MVD）。采用免疫组织化学法检测VEGF-A、VEGF-C和VEGF-D的表达；使用多变量分析模型研究生存分析及其独立作用。
LVD与肿瘤分级相关，但与pT分期无关。LVD与无转移生存期相关（对数秩检验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期的独立预测因素。虽然VEGF-C的表达与LVD和MVD均呈正相关，但VEGF-D仅与LVD相关。在单变量分析中，VEGF-A的表达与MVD相关，然而，它不是一个独立因素。
淋巴管生成和血管生成影响无转移生存期，并受VEGF-C和/或VEGF-D调节。我们的结果表明，LVD和MVD是选择膀胱癌患者术后管理和治疗策略的有用工具。
