Disrupted NOTCH activity is a driving event in urothelial bladder cancer (UBC). After activation by hypoxia, the NOTCH3 receptor participates in tumor cell proliferation, acquisition of the epithelial-mesenchymal transition phenotype, and angiogenesis. The aim was to analyze the association of NOTCH3 expression with histopathological and clinical parameters, and to determine its predictive impact on the clinical outcome in UBC patients. The present research included 614 UBC samples incorporated in paraffin tissue microarrays, evaluated by immunohistochemistry for NOTCH3 expression. The accrual period was four years, while the follow-up period was two years. The membranous expression was semi-quantified (0-3), and the mean degree was 1.81±0.94. Criteria for semi-quantification the NOTCH3 expression were the intensity of the staining and the percentage of positive cells. The samples with negative (0) and weak (1) NOTCH3 immunohistochemical (IHC) score were considered negative, while the samples that showed moderate (2) and strong (3) expression were considered positive. Higher degree of positivity was associated with higher risk of cancer-specific mortality (p<0.001). Independent predictors for cancer-specific mortality were NOTCH3 expression and high stage (p<0.001). NOTCH3 expression was not a statistically significant predictor of recurrence-free survival (p=0.816). This study indicated that NOTCH3 is a predictor of poor outcome, suggesting that the NOTCH3 could be potentially reliable IHC marker for selecting the UBC patients that would require more intensive follow-up, especially if they diagnosed in higher stage, with divergent differentiation in pathological report, and without recurrences which would lead them to more frequent medical assessments.

中文翻译：

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NOTCH3表达与膀胱尿路上皮癌患者临床结果的关系。

中断的 NOTCH 活动是膀胱尿路上皮癌 (UBC) 的驱动事件。在缺氧激活后，NOTCH3 受体参与肿瘤细胞增殖、获得上皮-间质转化表型和血管生成。目的是分析 NOTCH3 表达与组织病理学和临床参数的关联，并确定其对 UBC 患者临床结果的预测影响。本研究包括纳入石蜡组织微阵列的 614 个 UBC 样本，通过免疫组织化学评估 NOTCH3 表达。计提期为四年，跟踪期为两年。膜表达半定量(0-3)，平均度数为1.81±0.94。半定量NOTCH3表达的标准是染色强度和阳性细胞百分比。阴性 (0) 和弱 (1) NOTCH3 免疫组织化学 (IHC) 评分的样本被认为是阴性的，而表现出中度 (2) 和强 (3) 表达的样本被认为是阳性。较高程度的阳性与较高的癌症特异性死亡率风险相关（p<0.001）。癌症特异性死亡率的独立预测因子是 NOTCH3 表达和高分期 (p<0.001)。NOTCH3 表达不是无复发生存的统计学显着预测因子（p=0.816）。该研究表明，NOTCH3 是预后不良的预测因子，这表明 NOTCH3 可能是选择需要更密集随访的 UBC 患者的潜在可靠 IHC 标志物，