Laboratorio del Banco de Tumores, Instituto Universitario de Oncología del Principado de Asturias, Obra Social CajAstur, 33006 Oviedo, Asturias, Spain.
Lung Cancer. 2010 Sep;69(3):289-95. doi: 10.1016/j.lungcan.2009.12.010. Epub 2010 Jan 20.
The aim of our study was to determine the integrity of the cell-cell adhesion E-cadherin-beta-catenin complex in neuroendocrine lung tumors (NELTs) and the possible involvement of Snail in its deregulation.
The studied series consisted of formalin-fixed-paraffin-embedded tissue samples from 70 patients diagnosed with NELT (2000-2006) including tumors of low malignancy potential (3 tumorlets, 33 typical carcinoids), intermediate malignancy potential (3 atypical carcinoids) and tumors of high malignancy potential (10 large cell neuroendocrine carcinomas-LCNEC and 21 small cell carcinoma-SCLC). E-cadherin, beta-catenin and Snail expression were immunohistochemically evaluated and mRNA levels were assessed by Q-RT-PCR for E-cadherin and Snail.
Nuclear Snail signal was high in 46% tumors with the strongest level observed in high malignancy tumors. Furthermore, Snail levels correlated with tumor size, lymph node involvement and tobacco consumption. E-cadherin expression was downregulated in 24% cases and it was absent from the membrane in 31%, all of them cases of high malignancy potential. High E-cadherin levels and a membrane pattern were associated with tumor-free lymph node patients and inversely proportional to Snail protein expression. beta-catenin levels were weak in 43% and absent from the membrane in 59% cases. Interestingly, among high malignancy potential tumors, beta-catenin levels were significantly higher in LCNEC than in SCLC. The integrity of the E-cadherin-beta-catenin complex was retained in 37% cases, most of them carcinoid tumors, and correlated with low Snail levels, low malignancy potential and free lymph nodes.
Snail nuclear expression and loss of integrity of cell adhesion complex E-cadherin/beta-catenin parallels higher malignancy potential in NELTs.
我们研究的目的是确定神经内分泌肺肿瘤（NELTs）中细胞-细胞黏附 E-钙黏蛋白-β-连环蛋白复合物的完整性，以及 SNAI1 基因在其失调中的可能作用。
本研究纳入了 70 例经组织学证实的 NELTs 患者的福尔马林固定石蜡包埋组织标本（2000-2006 年），包括低恶性潜能肿瘤（3 例肿瘤细胞团，33 例典型类癌）、中恶性潜能肿瘤（3 例不典型类癌）和高恶性潜能肿瘤（10 例大细胞神经内分泌癌-LCNEC 和 21 例小细胞癌-SCLC）。应用免疫组化方法检测 E-钙黏蛋白、β-连环蛋白和 SNAI1 的表达，并用 Q-RT-PCR 检测 E-钙黏蛋白和 SNAI1 的 mRNA 水平。
46%的肿瘤细胞核中存在高信号的 SNAI1，在高恶性肿瘤中信号最强。此外，Snail 水平与肿瘤大小、淋巴结受累和吸烟有关。24%的病例中 E-钙黏蛋白表达下调，31%的病例 E-钙黏蛋白缺失，均为高恶性潜能肿瘤。高 E-钙黏蛋白水平和膜模式与无淋巴结转移的患者相关，与 Snail 蛋白表达呈负相关。43%的病例β-连环蛋白水平较弱，59%的病例β-连环蛋白缺失。有趣的是，在高恶性潜能肿瘤中，LCNEC 比 SCLC 中β-连环蛋白水平更高。E-钙黏蛋白-β-连环蛋白复合物的完整性在 37%的病例中保留，大部分为类癌肿瘤，与低 Snail 水平、低恶性潜能和无淋巴结转移相关。
Snail 核表达和细胞黏附复合体 E-钙黏蛋白/β-连环蛋白完整性缺失与 NELTs 的高恶性潜能平行。
