Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
Clin Cancer Res. 2012 Aug 1;18(15):4145-53. doi: 10.1158/1078-0432.CCR-12-0073. Epub 2012 Jun 6.
Vasohibin-1 (VASH1) is a novel angiogenic molecule that is specifically expressed in activated vascular endothelial cells, and the status of VASH1 expression has been documented in cancer angiogenesis. The aim of this study was to address the prognostic value of VASH1 expression in upper urinary tract urothelial carcinomas (UTUC).
We retrospectively analyzed the clinical records of 171 patients with locally advanced UTUC (Ta-3N0M0). The median follow-up period was 3.8 years. We immunohistochemically examined the accomplished microvessels with anti-CD34 as microvessel density (MVD) and the microvessels with activated endothelial cells as VASH1 density. Then, we analyzed the association between immunohistochemical expression and clinical outcomes.
Forty-two patients experienced tumor recurrence and of these 34 died of the disease during follow-up. VASH1 density was significantly associated with tumor grade, pathologic T stage, and MVD. The 5-year recurrence-free and cancer-specific survival rates were 66.1% and 72.8% in patients with VASH1 density (≥ 40/mm(2)) and 81.0% and 86.5% in their counterparts, respectively (P < 0.05). MVD was not an independent predictor of tumor recurrence or cancer-specific survival. Multivariate analyses revealed that high VASH1 density was an independent prognostic indicator of both tumor recurrence (P = 0.024, HR = 2.10) and cancer-specific survival (P = 0.031, HR = 2.23) as well as other standard prognostic factors including high tumor grade and lymphovascular invasion.
VASH1 density represents a clinically relevant predictor of patient prognosis in UTUC. The results suggest that VASH1 density could become a new biomarker and provide additional prognostic information in patients with UTUC.
血管生成抑制因子 1(VASH1)是一种新型的血管生成分子,特异性表达于活化的血管内皮细胞,其在肿瘤血管生成中的表达状态已有报道。本研究旨在探讨 VASH1 表达在上尿路尿路上皮癌(UTUC)中的预后价值。
我们回顾性分析了 171 例局部晚期 UTUC(Ta-3N0M0)患者的临床资料。中位随访时间为 3.8 年。我们采用抗 CD34 免疫组化法检测已完成的微血管作为微血管密度(MVD),并用激活的内皮细胞作为 VASH1 密度来检测微血管。然后,我们分析了免疫组化表达与临床结局之间的关系。
42 例患者出现肿瘤复发,其中 34 例在随访期间死于该疾病。VASH1 密度与肿瘤分级、病理 T 分期和 MVD 显著相关。VASH1 密度(≥40/mm²)患者的 5 年无复发生存率和癌症特异性生存率分别为 66.1%和 72.8%,而其对应值分别为 81.0%和 86.5%(P<0.05)。MVD 不是肿瘤复发或癌症特异性生存的独立预测因子。多因素分析显示,高 VASH1 密度是肿瘤复发(P=0.024,HR=2.10)和癌症特异性生存(P=0.031,HR=2.23)的独立预后指标,以及其他标准预后因素,包括高肿瘤分级和脉管侵犯。
VASH1 密度代表 UTUC 患者预后的一个有临床意义的预测因子。结果表明,VASH1 密度可能成为新的生物标志物,并为 UTUC 患者提供额外的预后信息。