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Combined aberrant expression of E-cadherin and S100A4, but not β-catenin is associated with disease-free survival and overall survival in colorectal cancer patients

Sang-Jeon Lee1, Song Yi Choi2, Wun-Jae Kim3, Meiying Ji4, Taek-Gu Lee1, Bo-Ra Son5, Soon Man Yoon4, Rohyun Sung2, Eun Jeoung Lee4, Sei Jin Youn4 and Seon Mee Park4*

Author affiliations

1 D1Department of Surgery, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Chungbuk 361-763, Republic of Korea

2 2Department of Pathology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

3 3Department of Urology, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

4 4Department of Internal Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

5 5Department of Laboratory Medicine, Chungbuk National University College of Medicine and Medical Research Institute, Cheongju, Republic of Korea

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Citation and License

Diagnostic Pathology 2013, 8:99  doi:10.1186/1746-1596-8-99

Published: 19 June 2013

Abstract

Background/Aims

Epithelial-to-mesenchymal transition (EMT) in cancers is related to metastasis, recurrence, and poor prognosis. We evaluated whether EMT-related proteins can act as prognostic biomarkers in colorectal cancer (CRC) patients.

Methods

We evaluated the expression of E-cadherin, β-catenin, and S100A4 by immunohistochemistry (IHC) in 333 CRC tissues from the tumor center and invasive margin. Tumor budding, cell grade, tumor stage, type of tumor growth, peritumoral lymphocyte infiltration (TLI), and perineural- or lymphovascular invasion were evaluated as pathological parameters. mRNA levels of E-cadherin, N-cadherin, β-catenin, and S100A4 from 68 specimens from the same set were analyzed by real time quantitative RT-PCR.

Results

Loss of E-cadherin, nuclear β-catenin, and gain of S100A4 were higher in the invasive margin than in the tumor center. Loss of E-cadherin was associated with cell grade, macroscopic type, perineural invasion, and tumor budding, β-catenin with microsatellite instability and tumor site, and S100A4 with growth type, macroscopic type, AJCC stage, lymphovascular invasion, and perineural invasion. The aberrant expression of E-cadherin and S100A4 not β-catenin in the invasive margin was a significant and independent risk factor for disease-free and overall-survival by multivariate analysis, along with AJCC stage and perineural invasion. mRNA levels of β-catenin and S100A4 were correlated with the IHC findings at the tumor invasive margin. E-cadherin and N-cadherin showed a weak inverse correlation.

Conclusions

The combination of loss of E-cadherin and gain of S100A4 in the tumor invasive margin can be used to stratify patients with the same AJCC stage into different survival groups.

Virtual slides

The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9398289629244673 webcite

Keywords:
Epithelial to mesenchymal transition; E-cadherin; β-catenin; S100A4; Tumor budding; Colorectal cancer