Fukuda S, Shirahama T, Imazono Y, Tsushima T, Ohmori H, Kayajima T, Take S, Nishiyama K, Yonezawa S, Akiba S, Akiyama S, Ohi Y
Department of Urology, Faculty of Medicine, Kagoshima University, Japan.
Cancer. 1999 Mar 15;85(6):1323-30.
Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor (PD-ECGF) are involved in increased angiogenic activity and disease progression in solid tumors. However, there is no information regarding the association of these angiogenic factors with clinicopathologic findings in testicular germ cell tumors (GCTs).
The authors examined the expression of VEGF and TP as well as microvessel density in GCTs and their association with clinicopathologic findings. Expression of VEGF and TP and microvessel density were examined immunohistochemically in 80 GCTs, including 33 seminomas (25 tumors with organ-confined disease and 8 with metastasis) and 47 nonseminomatous testicular GCTs (NSGCTs) (20 tumors with organ-confined disease and 27 with metastasis). Expression of VEGF also was examined in four GCTs and one nonneoplastic testis by immunoblotting.
VEGF protein was expressed more highly in GCTs compared with nonneoplastic testes. VEGF expression in GCTs was correlated significantly with microvessel count (P < 0.001). Both VEGF expression and microvessel count were correlated with metastasis in seminoma (P = 0.008 and P < 0.001, respectively), but only VEGF expression was identified as statistically significant by multiple regression analysis (P = 0.006). Conversely, four variables (VEGF expression, microvessel count, the presence of venous invasion, and the presence of embryonal carcinoma elements in the primary tumor) were correlated with metastasis in NSGCT (P < 0.001, P < 0.001, P = 0.004, and P = 0.029, respectively). However, multiple regression analysis revealed that only VEGF expression and microvessel count were significant factors for metastasis (P < 0.007 and P < 0.001, respectively). In contrast, high levels of TP were observed in infiltrating cells, but not in the majority of cancer cells.
The findings of the current study suggest that VEGF expression is involved in tumor development, angiogenesis, and metastasis in GCT.
血管生成对于肿瘤的生长和转移至关重要。血管内皮生长因子（VEGF）和胸苷磷酸化酶（TP）/血小板衍生内皮细胞生长因子（PD-ECGF）参与实体瘤血管生成活性增加和疾病进展。然而，关于这些血管生成因子与睾丸生殖细胞肿瘤（GCT）临床病理特征之间的关联尚无相关信息。
作者检测了GCT中VEGF和TP的表达以及微血管密度，并研究了它们与临床病理特征的关联。对80例GCT进行免疫组织化学检测VEGF和TP的表达以及微血管密度，其中包括33例精原细胞瘤（25例局限于器官的肿瘤和8例有转移的肿瘤）和47例非精原细胞性睾丸GCT（NSGCT）（20例局限于器官的肿瘤和27例有转移的肿瘤）。还通过免疫印迹法检测了4例GCT和1例非肿瘤性睾丸中VEGF的表达。
与非肿瘤性睾丸相比，GCT中VEGF蛋白表达更高。GCT中VEGF表达与微血管计数显著相关（P < 0.001）。VEGF表达和微血管计数在精原细胞瘤中均与转移相关（分别为P = 0.008和P < 0.001），但多元回归分析仅VEGF表达具有统计学意义（P = 0.006）。相反，四个变量（VEGF表达、微血管计数、静脉侵犯的存在以及原发肿瘤中胚胎癌成分的存在）与NSGCT转移相关（分别为P < 0.001、P < 0.001、P = 0.004和P = 0.029）。然而，多元回归分析显示只有VEGF表达和微血管计数是转移的重要因素（分别为P < 0.007和P < 0.001）。相比之下，在浸润细胞中观察到高水平的TP，但大多数癌细胞中未观察到。
本研究结果表明VEGF表达参与了GCT的肿瘤发生、血管生成和转移。
