Nuclear Expression of Snail Is an Independent Negative Prognostic Factor in Human Breast Cancer

S Muenst,S Däster,S D Soysal,R A Droeser,W P Weber,F Gao,D Oertli,E C Obermann,U Von Holzen,C Viehl

doi:10.1155/2013/902042

Abstract

Background. Snail is a key regulator of epithelial-mesenchymal transition of tumor cells. Several studies have shown nuclear Snail expression to be a negative prognostic factor in human cancer, where it is generally associated with more aggressive tumor behavior and worse survival. Objectives and Methods. To further explore the role of Snail expression in breast cancer, we conducted a study on a tissue microarray, encompassing 1043 breast cancer cases. Results. A total of 265 (25.4%) breast cancers were positive for Snail. Snail expression was significantly associated with greater tumor size, higher tumor stage and grade, positive lymph node status, and hormone receptor negative status and was differently expressed in the intrinsic subtypes of breast cancer, being the highest in the basal-like subtype and the lowest in the luminal A subtype. In multivariate analysis, Snail proved to be an independent negative prognostic factor for OS. In the intrinsic subtypes, Snail expression was a negative prognostic factor for OS in the luminal B HER2−, the luminal B HER2+, and the basal-like subtype. Conclusions. This is the first study demonstrating that nuclear Snail expression is an independent negative predictor of prognosis in breast cancer, thus suggesting that it may represent a potential therapeutic target.

Highlights

Snail, a zinc finger transcription factor, is a key regulator of epithelial-mesenchymal transition (EMT) of epithelial tumor cells [1]
Snail expression was significantly associated with greater tumor size, higher tumor stage and grade, positive lymph node status, and hormone receptor negative status and was differently expressed in the intrinsic subtypes of breast cancer, being the highest in the basal-like subtype and the lowest in the luminal A subtype
Since 42.6% of cases with nuclear Snail expression were in the 5% and 10% categories, we decided that a cutoff set at ≥5% represents the most appropriate threshold

Summary

Introduction

A zinc finger transcription factor, is a key regulator of epithelial-mesenchymal transition (EMT) of epithelial tumor cells [1]. It directly represses transcription of the cell adhesion molecule E-cadherin while inducing transcription of mesenchymal genes [2, 3]. Several studies have shown nuclear Snail expression to be a negative prognostic factor in human cancer, where it is generally associated with more aggressive tumor behavior and worse survival. This is the first study demonstrating that nuclear Snail expression is an independent negative predictor of prognosis in breast cancer, suggesting that it may represent a potential therapeutic target

Objectives

Methods

Results

Discussion

Conclusion