Harb Ola A, Elfeky Mariem A, El Shafaay Basant Sh, Taha Heba F, Osman Gamal, Harera Ibtsam Shehta, Gertallah Loay M, Abdelmonem Doaa Metwaly, Embaby Ahmed
Department of Pathology, Zagazig University, Faculty of Medicine, Zagazig, Egypt.
Department of Clinical Oncology and Nuclear Medicine, Faculty of Medicine, Zagazig, Egypt.
Pathophysiology. 2018 Dec;25(4):335-345. doi: 10.1016/j.pathophys.2018.05.004. Epub 2018 May 18.
Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane.
Was to assess the tissue protein markers SPOP, ZEB1 & E-cadherin expressions in benign areas of neoplastic kidney specimens and in cc-RCC patients, then correlating their expression levels with patients clinicopathological and prognostic data.
We evaluated SPOP, ZEB-1 & E-cadherin expression using immunohistochemistry in samples from 50 cc-RCC and 20 benign areas of neoplastic kidney specimens, then we followed our patients for 5 years and finally we have analyzed correlations between the levels of markers expressions with patients clinicopathological and prognostic criteria in cc-RCC.
Positive expression of SPOP & ZEB1 in addition to negative E- cadherin expression was detected in cc-RCC more than benign areas of neoplastic kidney specimens (p = 0.004 and p < 0.001 respectively). In cc-RCC Positive expression of SPOP, ZEB1 and negative E- cadherin expression was associated with higher grade (p = 0.006, 0.007 & <0.001 respectively), advanced AJCC stage (p = 0.013, 0.023 & <0.001 respectively), presence of L.N metastases (p = 0.002 = 0.010 and <0.001 respectively), distant metastases (p = 0.001, 0.003 & 0.035 respectively), poor PFS and OS rates (p < 0.001 and p = 0.013 respectively).
Positive expression of SPOP& ZEB1 in addition to negative E- cadherin are associated with poor prognosis in cc-RCC patients.
透明细胞肾细胞癌（cc-RCC）在致死率、转移倾向和化疗耐药性方面是一种严重的癌症，因此需要确定新的治疗靶点以改善患者预后。SPOP是一种含有BTB/POZ结构域的斑点型POZ蛋白，已被鉴定为E3泛素连接酶成分。ZEB1是上皮-间质转化（EMT）的关键激活因子；E-钙黏蛋白是一种在正常上皮细胞膜中检测到的细胞黏附蛋白。
评估肿瘤性肾标本良性区域以及cc-RCC患者中组织蛋白标志物SPOP、ZEB1和E-钙黏蛋白的表达情况，然后将它们的表达水平与患者的临床病理和预后数据相关联。
我们采用免疫组织化学方法评估了50例cc-RCC样本和20例肿瘤性肾标本良性区域样本中SPOP、ZEB-1和E-钙黏蛋白的表达，随后对患者进行了5年随访，最后分析了cc-RCC中标志物表达水平与患者临床病理及预后标准之间的相关性。
与肿瘤性肾标本良性区域相比，cc-RCC中检测到SPOP和ZEB1的阳性表达以及E-钙黏蛋白的阴性表达（分别为p = 0.004和p < 0.001）。在cc-RCC中，SPOP、ZEB1的阳性表达以及E-钙黏蛋白的阴性表达与更高的分级（分别为p = 0.006、0.007和<0.001）、美国癌症联合委员会（AJCC）晚期分期（分别为p = 0.013、0.023和<0.001）、淋巴结转移的存在（分别为p = 0.002、0.01和<0.001）、远处转移（分别为p = 0.001、0.003和0.035）、较差的无进展生存期（PFS）和总生存期（OS）率（分别为p < 0.001和p = 0.013）相关。
SPOP和ZEB1的阳性表达以及E-钙黏蛋白的阴性表达与cc-RCC患者的不良预后相关。
