Slug is overexpressed in gastric carcinomas and may act synergistically with SIPI and Snail in the down-regulation of E-cadherin

Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is known to play an important role in tumour progression. The aim of our study was to investigate the mRNA expression of two EMT regulators - Slug and E12IE47 - in primary human gastric carcinomas and to compare this with the expression of E-cadhetin and other EMT regulators (Snail, Twist, and SIP1). We studied a series of 59 gastric carcinomas by real-time quantitative RT-PCR in formalin-fixed and paraffin-embedded tissues. Thirty-four cases (58%) showed Slug up-regulation in the tumour; reduced or negative expression of E-cadherin was present in 24 of these (71%, p < 0.0001). Twenty-one cases (36%) showed E12IE47 up-regulation that was not significantly associated with E-cadherin down-regulation (p = 0.5734). Slug up-regulation accompanied by E-cadherin down-regulation correlated with the presence of distant metastases (p = 0.0029) and with advanced pTNM stages (p = 0.0424). A statistically significant association was found between Slug up-regulation and the expression of SIP1 in intestinal (p = 0.0014) and Snail in diffuse (p = 0.0067) carcinomas. We present the first study integrating the analysis of several EMT regulators in primary gastric carcinomas and conclude that Slug up-regulation is associated with E-cadherin down-regulation in diffuse and intestinal-type gastric carcinoma, and that this effect could be complemented by the presence of other EMT regulators. Copyright (c) 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.