Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors

Introduction: 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. Methods: The studied series consisted of formalin-fixed-paraffin-embedded tissue samples from 70 patients diagnosed with NELT (2000-2006) including tumors of low malignacy 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. Results: 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. Conclusion: Snail nuclear expression and loss of integrity of cell adhesion complex E-cadherin/beta-catenin parallels higher malignancy potential in NELTs. (C) 2009 Elsevier Ireland Ltd. All rights reserved.