결직장샘암종에서 Slug, Twist 발현과 E-cadherin발현의 의의

Abstract

Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is thought to play a fundamental role during early steps of invasion and metastasis of carcinoma cells. There are several EMT regulators including Snail, SIP1 (both are direct repressors of E-cadherin), and Twist (an activator of N-cadherin during Drosophila embryogenesis). Twist, a basic helix-loop-helix (bHLH) transcription factor, is a master regulator of gastrulation and mesoderm specification , and has now been characterized as a newly found EMT-inducer and has been shown to be involved in tumor invasiveness and metastasis. Slug, a member of the Snail family of transcription factors, plays a crucial role in the regulation of EMT by suppressing several epithelial markers and adhesion molecules including E-cadherin. The purpose of the present study was to examine the significance between expression of Twist and Slug and clinicopathological parameters in colorectal adenocarcinoma (CRA) as determined by immunohistochemical analysis and the correlation between Twist, Slug and E-cadherin expression in CRA. Moreover, to elucidate whether Twist and Slug may be used as a novel parameter to predict prognosis in CRA. A semiquantitative scoring system was applied based on the intensity and extent of positive immunohistochemical staining. Twist and Slug expression was significantly related to tumor invasion depth (p=0.001, p=0.019, respectively), and showed inverse correlation with expression of E-cadherin (p=0.045, p<0.001, respectively). However, Twist and Slug did not influence overall survival. These results demonstrated that a positive role of Slug and Twist in tumor invasion in CRA, and inverse correlation between Twist and Slug expression and E-cadherin expression suggest that Twist and Slug may play some role in the EMT by inhibition of E-cadherin activity.