Shah Carl-Henrik, Viktorsson Kristina, Kanter Lena, Sherif Amir, Asmundsson Jurate, Rosenblatt Robert, Lewensohn Rolf, Ullén Anders
Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden.
Urol Oncol. 2014 Nov;32(8):1215-24. doi: 10.1016/j.urolonc.2014.04.015. Epub 2014 May 28.
A major challenge in muscle-invasive urothelial carcinoma (UC) is to identify biomarkers that can predict disease prognosis and treatment response after cystectomy. Therefore, we analyzed the potential prognostic value of the proteins vascular endothelial growth factor receptor 2 (VEGFR2), S100A4, and S100A6 in UC.
Retrospective outcome data and tumor specimens from 83 cystectomy patients with histologically confirmed invasive UC were included. Expression levels of VEGFR2 (also called flk-1 and KDR), S100A4, and S100A6 were analyzed in primary tumor tissue by immunohistochemistry.
Immunohistochemical staining and analysis of VEGFR2, S100A4, and S100A6 showed localization mainly in tumor cell cytoplasm. High VEGFR2 expression and low tumor category were independent variables associated with longer overall survival (OS) and disease-free survival, revealed by a bivariate Cox proportional hazards regression model (both P<0.001). In addition, the univariate log-rank test and the Cox model demonstrated that OS beyond 2 years was significantly greater among patients with low S100A6 expression than in those with high S100A6 expression (P = 0.017 and 0.022, respectively). Differences in tumor expression of S100A4 were not significantly associated with outcome.
In this study, VEGFR2 expression was significantly correlated with risk of disease relapse and OS in a defined cohort of patients with UC of the bladder treated by cystectomy.
肌肉浸润性尿路上皮癌（UC）的一个主要挑战是识别能够预测膀胱切除术后疾病预后和治疗反应的生物标志物。因此，我们分析了血管内皮生长因子受体2（VEGFR2）、S100A4和S100A6蛋白在UC中的潜在预后价值。
纳入83例经组织学确诊为浸润性UC的膀胱切除患者的回顾性结局数据和肿瘤标本。通过免疫组织化学分析原发性肿瘤组织中VEGFR2（也称为flk-1和KDR）、S100A4和S100A6的表达水平。
VEGFR2、S100A4和S100A6的免疫组织化学染色及分析显示其主要定位于肿瘤细胞胞质。二元Cox比例风险回归模型显示，高VEGFR2表达和低肿瘤分级是与更长总生存期（OS）和无病生存期相关的独立变量（均P<0.001）。此外，单因素对数秩检验和Cox模型表明，S100A6低表达患者的2年以上OS显著高于S100A6高表达患者（分别为P = 0.017和0.022）。S100A4的肿瘤表达差异与结局无显著相关性。
在本研究中，在一组接受膀胱切除术治疗的UC患者中，VEGFR2表达与疾病复发风险和OS显著相关。
