Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma
Epithelial-mesenchymal transformation markers E-cadherin and survivin predict progression of stage pTa urothelial bladder carcinoma
复制标题
DOI：
10.1007/s00345-015-1690-5
复制
发表时间：
2016-05-01
影响因子：
3.4
通讯作者：
Otto, Wolfgang
中科院分区：
文献类型：
--
作者：
Breyer, Johannes;Gierth, Michael;Otto, Wolfgang
为了确定免疫组化标记物生存素和E-钙粘蛋白是否可以预测在最初诊断的Ta膀胱癌的进展，我们回顾性地搜索了从1992年1月至2004年12月在德国的单中心医院治疗的每一个最初诊断的pTa尿路上皮膀胱癌。随访记录至2010年6月，以复发或进展为终点。对TURB标本进行Survivin和E-cadherin的免疫组化染色和分析。采用单因素和多因素回归分析、Kaplan-Meier分析、单因素和多因素考克斯回归分析，对免疫组化染色的进展和无进展的结局依赖性进行分析。其中42%的患者在随访TURB中无肿瘤，46%的患者至少有一次pTa复发，12%的患者甚至进展为至少pT 1膀胱癌。在71%的进展患者中发现E-钙粘蛋白的异常染色，而在无进展的病例中仅为40%（p = 0.004）。在所有进展的患者中，92%的患者在其初始pTa标本中显示生存素过表达，相比之下，61%的患者没有进展（p = 0.001）。Kaplan-Meier分析显示异常的E-钙粘蛋白染色与更差的无进展生存期（PFS）（p = 0.005）以及生存素过度表达（p = 0.003）相关。在多变量考克斯回归分析中，E-cadherin强染色是PFS较好的独立指标（p = 0.033）和多灶性（p = 0.046）和肿瘤大小超过3 cm（p = 0.042）是PFS恶化的预测因子。钙粘蛋白可以帮助识别处于发展为早期pTa膀胱癌的进展性疾病的风险中的患者。
To determine whether the immunohistochemical markers survivin and E-cadherin can predict progress at initially diagnosed Ta bladder cancer.We retrospectively searched for every initially diagnosed pTa urothelial bladder carcinoma having been treated at our single-center hospital in Germany from January 1992 up to December 2004. Follow-up was recorded up to June 2010, with recurrence or progress being the endpoints. Immunohistochemical staining and analysis of survivin and E-cadherin of the TURB specimens were performed. Outcome dependency of progression and no progression with immunohistochemical staining was analyzed using uni- and multivariate regression analysis, Kaplan-Meier analysis and uni- and multivariate Cox regression analysis.Overall, 233 patients were included. Forty-two percent of those were tumor free in their follow-up TURBs, 46 % had at least one pTa recurrence and 12 % even showed progress to at least pT1 bladder cancer. Aberrant staining of E-cadherin was found within 71 % of patients with progression in contrast to only 40 % in cases without progression (p = 0.004). Of all progressed patients, 92 % showed overexpression of survivin in their initial pTa specimen compared to 61 % without progression (p = 0.001). Kaplan-Meier analysis revealed aberrant E-cadherin staining to be associated with worse progression-free survival (PFS) (p = 0.005) as well as overexpression of survivin (p = 0.003). In multivariate Cox regression analysis, strong E-cadherin staining was an independent prognosticator for better PFS (p = 0.033) and multifocality (p = 0.046) and tumor size over 3 cm (p = 0.042) were prognosticators for worse PFS.Adding the immunohistochemical markers survivin and E-cadherin could help to identify patients at risk of developing a progressive disease in initial stage pTa bladder cancer.