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Snail nuclear expression parallels higher malignancy potential in neuroendocrine lung tumors

J A Galván1, M V González, G Crespo

  • 1Laboratorio del Banco de Tumores, Instituto Universitario de Oncología del Principado de Asturias, Obra Social CajAstur, 33006 Oviedo, Asturias, Spain.

Lung Cancer (Amsterdam, Netherlands)
|January 22, 2010
PubMed
Abstract

Insights

Snail protein disrupts the E-cadherin-beta-catenin complex in neuroendocrine lung tumors (NELTs), correlating with higher tumor malignancy. Preserving this complex indicates lower malignancy and better outcomes in NELTs.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Pathology

Background:

  • Neuroendocrine lung tumors (NELTs) are a heterogeneous group of neoplasms.
  • The E-cadherin-beta-catenin complex is crucial for cell-cell adhesion and its disruption is implicated in cancer progression.
  • The role of Snail, a transcription factor, in regulating this complex in NELTs is not fully understood.

Purpose of the Study:

  • To investigate the integrity of the E-cadherin-beta-catenin complex in various types of NELTs.
  • To determine the correlation between the expression of Snail and the integrity of this complex.
  • To assess the potential involvement of Snail in the deregulation of cell-cell adhesion in NELTs.

Main Methods:

  • Immunohistochemical analysis of E-cadherin, beta-catenin, and Snail expression in 70 NELT tissue samples.
  • Quantitative real-time PCR (Q-RT-PCR) to assess mRNA levels of E-cadherin and Snail.
  • Categorization of NELTs based on malignancy potential: low (tumorlets, typical carcinoids), intermediate (atypical carcinoids), and high (large cell neuroendocrine carcinoma, small cell carcinoma).

Main Results:

  • High nuclear Snail expression was observed in 46% of tumors, particularly in high malignancy potential NELTs.
  • E-cadherin downregulation and loss of membrane expression were frequent in high malignancy tumors and inversely correlated with Snail levels.
  • Loss of E-cadherin-beta-catenin complex integrity was found in 63% of cases and correlated with high Snail levels, high malignancy, and lymph node involvement.

Conclusions:

  • Increased nuclear Snail expression is associated with the loss of E-cadherin-beta-catenin complex integrity in NELTs.
  • Disruption of this cell adhesion complex parallels a higher malignancy potential in neuroendocrine lung tumors.
  • These findings suggest Snail is a key factor in the progression of NELTs.

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