OBJECTIVE Aberrant expression of cadherins is known to be associated with tumor aggression. However, their role in clear cell renal cell carcinoma (CCRCC) is not well elucidated. This study investigated the expression of epithelial cadherin (E-cadherin), neural cadherin (N-cadherin), and placental cadherin (P-cadherin) in CCRCC, and assessed their prognostic significance and clinicopathologic association. MATERIALS AND METHODS We enrolled 254 patients with CCRCC who underwent radical or partial nephrectomy. E-cadherin, N-cadherin, and P-cadherin expression was evaluated by immunohistochemistry in a tissue microarray. RESULTS Low E-cadherin expression was associated with larger tumor size, lymphovascular invasion, higher pT stage, lymph node and distant metastasis, and higher stage. High N-cadherin expression was significantly associated with larger tumor size, higher nuclear grade, and tumor necrosis. P-cadherin expression was found to be significantly associated with higher nuclear grade, distant metastasis, and higher stage. Univariate analysis revealed that aberrant expression of the 3 cadherins was significantly related to shorter overall survival (OS). Loss of E-cadherin, high P-cadherin expression, and higher stage were independent prognostic factors for OS. For recurrence-free survival, lymphovascular invasion, high P-cadherin expression, and higher stage were independent prognostic factors. Cadherin switch was significantly associated with aggressive clinicopathologic factors and poor outcomes. CONCLUSIONS Aberrant expression of E-cadherin, N-cadherin, and P-cadherin was associated with adverse clinicopathologic factors and worse OS. Low E-cadherin and high P-cadherin expression were significantly associated with distant metastasis and independent prognostic factors. Therefore, cadherin expression may be used as a prognostic marker and therapeutic target, and cadherin switch plays an important role in CCRCC progression.

中文翻译：

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E-cadherin、N-cadherin和P-cadherin在肾透明细胞癌中的异常表达

目的 已知钙粘蛋白的异常表达与肿瘤侵袭有关。然而，它们在透明细胞肾细胞癌 (CCRCC) 中的作用尚未得到很好的阐明。本研究调查了 CCRCC 中上皮钙粘蛋白 (E-cadherin)、神经钙粘蛋白 (N-cadherin) 和胎盘钙粘蛋白 (P-cadherin) 的表达，并评估了它们的预后意义和临床病理学关联。材料与方法 我们招募了 254 名接受根治性或部分肾切除术的 CCRCC 患者。E-钙粘蛋白、N-钙粘蛋白和 P-钙粘蛋白的表达通过组织微阵列中的免疫组织化学进行评估。结果 低 E-cadherin 表达与更大的肿瘤大小、淋巴血管浸润、更高的 pT 分期、淋巴结和远处转移以及更高的分期有关。高 N-钙粘蛋白表达与较大的肿瘤大小、较高的核分级和肿瘤坏死显着相关。发现 P-钙粘蛋白表达与更高的核分级、远处转移和更高的分期显着相关。单变量分析显示，3 种钙粘蛋白的异常表达与较短的总生存期 (OS) 显着相关。E-cadherin 的缺失、P-cadherin 的高表达和更高的分期是 OS 的独立预后因素。对于无复发生存，淋巴血管浸润、高 P-钙粘蛋白表达和更高的分期是独立的预后因素。钙粘蛋白转换与侵袭性临床病理因素和不良结局显着相关。结论 E-钙粘蛋白、N-钙粘蛋白、P-cadherin 与不利的临床病理因素和较差的 OS 相关。低 E-cadherin 和高 P-cadherin 表达与远处转移和独立预后因素显着相关。因此，钙粘蛋白表达可作为预后标志物和治疗靶点，钙粘蛋白开关在 CCRCC 进展中起重要作用。