Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors

Galván, J.A.; González, M.V.; Crespo, G.; Folgueras, M.V.; Astudillo, A.

doi:10.1016/j.lungcan.2009.12.010

« Previous Next »Lung Cancer
Volume 69, Issue 3 , Pages 289-295, September 2010

Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors

J.A. Galván
- Laboratorio del Banco de Tumores, Instituto Universitario de Oncología del Principado de Asturias, Obra Social CajAstur (IUOPA), c/Celestino Villamil s/n, 33006 Oviedo, Asturias, Spain
M.V. González
- Oncologia Quirúrgica, Instituto Universitario de Oncologia del Principado de Asturias, Obra Social CajAstur (IUOPA), c/Celestino Villamil s/n, 33006 Oviedo, Asturias, Spain
G. Crespo
- Servicio de Oncología Médica, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain
M.V. Folgueras
- Servicio de Anatomia Patológica, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain
A. Astudillo
- Laboratorio del Banco de Tumores, Instituto Universitario de Oncología del Principado de Asturias, Obra Social CajAstur (IUOPA), c/Celestino Villamil s/n, 33006 Oviedo, Asturias, Spain
- Servicio de Anatomia Patológica, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain
- Corresponding author at: Servicio de Anatomía Patológica, Hospital Universitario Central de Asturias, 33006 Oviedo, Spain. Tel.: +34 985107891.

Received 24 September 2009; received in revised form 9 December 2009; accepted 18 December 2009. published online 21 January 2010.

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.