Institute of Pathology, Faculty of Medicine, University of Belgrade, 1 Dr. Subotic Street, 11000 Belgrade, Serbia.
Department of Pathological Physiology, Faculty of Medicine, University of Belgrade, 9 Dr. Subotic Street, 11000 Belgrade, Serbia.
Int J Mol Sci. 2023 Jul 31;24(15):12245. doi: 10.3390/ijms241512245.
Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial-mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan-Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor ( = 0.046). The expression of Snail was associated with higher stages of the disease ( = 0.004), especially observing nuclear Snail expression ( < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity ( < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression ( = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer.
肾细胞癌(RCC)是最致命的泌尿系统肿瘤。迄今为止,临床指南中并未纳入任何经过验证的生物标志物用于筛选和随访 RCC 患者。Slug(Snail2)和 Snail(Snail1)属于 Snail 锌指转录因子超家族,参与上皮-间充质转化,这一过程在胚胎发生中很重要,但也与肿瘤进展有关。我们检查了不同分期的肾细胞癌患者的 Slug 和 Snail 免疫组织化学表达,旨在研究它们作为分期和预后因素的潜在作用。使用组织微阵列和免疫组织化学分析了 166 例恶性肾细胞肿瘤样本。评估 Slug 和 Snail 表达的定性(存在或不存在),在核和细胞质细胞区室中,并与临床参数进行比较。Kaplan-Meier 生存分析显示肉瘤样成分和 Slug 表达对生存时间的影响。Cox 回归分析将 Slug 作为唯一独立的预后因素( = 0.046)。Snail 的表达与疾病的较高分期相关( = 0.004),尤其是观察到核 Snail 表达( < 0.001)。所有发生转移的肿瘤均显示核免疫反应性( < 0.001)。在透明细胞 RCC 中,我们显示核分级高与核 Snail 表达之间存在显著关系( = 0.039)。我们的结果表明,Slug 和 Snail 可能是各种 RCC 患者分期和预后的有用免疫组织化学标志物,代表了肾癌进一步治疗策略的潜在靶点。