Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors

Abstract

Introduction The aim of our study was to determine the integrity of the cell–cell adhesion E-cadherin–β-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, β-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. β-catenin levels were weak in 43% and absent from the membrane in 59% cases. Interestingly, among high malignancy potential tumors, β-catenin levels were significantly higher in LCNEC than in SCLC. The integrity of the E-cadherin–β-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/β-catenin parallels higher malignancy potential in NELTs.