1693P - Clinical implication of epithelial to mesenchymal transition in hepatocellular carcinoma

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Hepatobiliary Cancers
Pathology/Molecular Biology
Presenter Tsutomu Fujii
Authors T. Fujii1, S. Yamada2, N. Okumura2, B.C. Fuchs3, M. Suenaga4, G. Nakayama5, H. Sugimoto2, S. Takeda2, K.K. Tanabe3, Y. Kodera1
  • 1Department Of Surgery Ii, Nagoya University Graduate School of Medicine, 466-8550 - Nagoya/JP
  • 2Department Of Gastroenterological Surgery (surgery Ii), Nagoya University Graduate School of Medicine, 466-8550 - Nagoya/JP
  • 3Division Of Surgical Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston/US
  • 4Gastroenterological Surgery (surgery Ii) Dept., Nagoya University Graduate School of Medicine, 466-8550 - Nagoya/JP
  • 5Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 466-8550 - Nagoya/JP

Abstract

Background

Epithelial-to-mesenchymal transition (EMT) was originally proposed as a process of organogenesis. In recent years, the association between EMT and cancer invasion and metastasis has been advocated and actively investigated in various cancers. In addition, chemoresistance and cancer stemness could be involved in EMT, and the elucidation of this association might contribute to improved outcomes of hepatocellular carcinoma (HCC). We utilized surgical specimens of HCC from our department to examine the clinical implications of EMT.

Methods

One hundred and one patients with hepatocellular carcinoma, who underwent resection in our department between 1994 and 2003 were analyzed. The mRNA expression of E-cadherin and Vimentin were measured by quantitative real-time PCR and EMT status of each patient was determined as follows: Vimentin/E-cadherin < 2 = Epithelial (E), Vimentin/E-cadherin ≥ 2 = Mesenchymal (M). Moreover, transcription factors which are involved in EMT (Twist, Snail, Slug, Zeb-1, and Zeb-2) and also IL-6 and its receptor IL-6R were measured. The correlation between these values and clinicopathological factors and prognosis were analyzed statistically.

Results

1) AFP values were significantly higher in the epithelial group than in the mesenchymal group (P = 0.029). There was no difference in overall survival, but a significant difference was found in disease-free survival (P = 0.042), which showed that patients with a mesenchymal tumor were more prone to have an earlier recurrence than those with an epithelial tumor. 2) All transcription factors were more highly expressed in mesenchymal than in epithelial tumors, and in particular, Twist and Zeb-2 were significantly overexpressed (P = 0.0002, P = 0.0017, respectively). 3) IL-6 expression was also significantly higher in mesenchymal than in epithelial tumors, but there was no difference in IL-6R expression.

Discussion

Our study using resected surgical specimens suggest that EMT could be involved in cancer invasion and metastasis at the clinical level. In particular, Twist and Zeb-2 might be important for inducing EMT in HCC and patients with mesenchymal tumors are more prone to have early recurrence or metastases after resection. In addition, IL-6 might be an important factor for HCC EMT and could be a potential therapeutic target.

Disclosure

All authors have declared no conflicts of interest.