核 E-钙黏蛋白表达与膜 E-钙黏蛋白的丢失、浆细胞样分化以及膀胱癌的总体生存时间缩短有关。
Nuclear E-cadherin expression is associated with the loss of membranous E-cadherin, plasmacytoid differentiation and reduced overall survival in urothelial carcinoma of the bladder.
机构信息
Department of Urology, University Hospital Erlangen, Erlangen, Germany.
出版信息
Ann Surg Oncol. 2013 Jul;20(7):2440-5. doi: 10.1245/s10434-012-2709-4. Epub 2012 Oct 30.
BACKGROUND
Loss of E-cadherin represents a hallmark of plasmacytoid differentiation. We analyzed the effect of membranous E-cadherin loss and its nuclear accumulation in patients with locally advanced conventional urothelial carcinoma (UC) who were treated with radical cystectomy and adjuvant chemotherapy.
METHODS
A total of 247 formalin-fixed, paraffin-embedded tumor samples were reviewed to detect histological variants of UC. Immunohistochemical staining of E-cadherin was performed and analyzed for membranous and nuclear expression. The correlation between E-cadherin expression and histology was assessed, and overall survival (OS) was analyzed with univariate and multivariate Cox regression and Kaplan-Meier analyses. Correlation of nuclear E-cadherin to tumor stage (pT), lymph node metastasis (pN), histologic subtype, and chemotherapy was performed by Fisher's exact test.
RESULTS
Membranous and nuclear E-cadherin expression was strongly correlated to plasmacytoid urothelial carcinoma (PUC) (p < 0.001). Complete loss of membranous E-cadherin expression was observed in 76.2 % of PUCs, 11.1 % of conventional UCs, and 0 % of micropapillary urothelial carcinoma (MPCs). Nuclear accumulation was found in 47.6 % of PUCs, 10 % of MPCs, and 1.8 % of UCs. Sixty-two percent of all tumors with negative membranous E-cadherin expression and nuclear accumulation were PUCs (p = 0.035). In a Kaplan-Meier analysis, mean survival with nuclear E-cadherin expression was 31.9 months [95 % confidence interval (CI) 16.1-47.6] of patients without nuclear staining 61 months (95 % CI 53.5-67.7; p = 0.045). A univariate Cox regression analysis showed that nuclear E-cadherin accumulation was associated with a 2-fold increase in risk of death (95 % CI 1.03-4.06; p = 0.04). In multivariate Cox regression analysis adjusted to type of chemotherapy, tumor stage, and tumor grade, the hazard ratio for patients with nuclear E-cadherin was 2.03 (95 % CI 1.00-4.121; p = 0.050).
CONCLUSIONS
Nuclear E-cadherin is associated with PUCs and is suggested to be an independent prognostic factor in advanced UC.
背景
E-钙黏蛋白的丢失代表浆细胞样分化的一个标志。我们分析了在接受根治性膀胱切除术和辅助化疗的局部晚期常规尿路上皮癌（UC）患者中，膜E-钙黏蛋白丢失及其核内积聚的影响。
方法
共回顾了 247 例福尔马林固定、石蜡包埋的肿瘤样本，以检测 UC 的组织学变异。进行 E-钙黏蛋白的免疫组织化学染色，并分析其膜和核表达。评估 E-钙黏蛋白表达与组织学之间的相关性，并通过单变量和多变量 Cox 回归和 Kaplan-Meier 分析进行总生存期（OS）分析。通过 Fisher 精确检验对核 E-钙黏蛋白与肿瘤分期（pT）、淋巴结转移（pN）、组织学亚型和化疗之间的相关性进行分析。
结果
膜和核 E-钙黏蛋白的表达与浆细胞样尿路上皮癌（PUC）呈强相关（p<0.001）。76.2%的 PUC 完全丢失膜 E-钙黏蛋白表达，11.1%的常规 UC 和 0%的微乳头状尿路上皮癌（MPC）。核内积聚见于 47.6%的 PUC、10%的 MPC 和 1.8%的 UC。所有膜 E-钙黏蛋白表达阴性和核内积聚的肿瘤中，62%为 PUC（p=0.035）。在 Kaplan-Meier 分析中，核 E-钙黏蛋白表达的中位生存时间为 31.9 个月[95%置信区间（CI）16.1-47.6]，无核染色的患者为 61 个月[95%CI 53.5-67.7;p=0.045]。单变量 Cox 回归分析显示，核 E-钙黏蛋白积聚与死亡风险增加 2 倍相关（95%CI 1.03-4.06;p=0.04）。在调整化疗类型、肿瘤分期和肿瘤分级的多变量 Cox 回归分析中，核 E-钙黏蛋白患者的危险比为 2.03（95%CI 1.00-4.121;p=0.050）。
结论
核 E-钙黏蛋白与 PUC 相关，并提示在晚期 UC 中是一个独立的预后因素。
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