Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: Clinicopathological significance

Choi,Ji Eun; Bae,Jun Sang; Kang,Myoung Jae; Chung,Myoung Ja; Jang,Kyu Yun; Park,Ho Sung; Moon,Woo Sung

doi:10.3892/or.2017.5790

Expression of epithelial-mesenchymal transition and cancer stem cell markers in colorectal adenocarcinoma: Clinicopathological significance

Authors:
- Ji Eun Choi
- Jun Sang Bae
- Myoung Jae Kang
- Myoung Ja Chung
- Kyu Yun Jang
- Ho Sung Park
- Woo Sung Moon
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Affiliations: Department of Pathology, Daejeon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Jung-gu, Daejeon 34943, Republic of Korea, Department of Pathology, Chonbuk National University, Medical School, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital and Research Institute for Endocrine Sciences, Jeonju 561-756, Republic of Korea
Published online on: July 5, 2017 https://doi.org/10.3892/or.2017.5790
Pages: 1695-1705

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Abstract

Epithelial-mesenchymal transition (EMT) is known to be associated with cancer progression, metastatic spread, and therapeutic resistance and to occur at the invasive front. Cancer stem cells (CSCs) display stemness features and might be implicated in tumor initiation, local recurrence and metastasis. The present study was conducted to examine the expression status and relationships between EMT- and CSC-related proteins in the different tumor areas of primary colorectal cancer (CRC), along with their clinicopathological significance. We performed immunohistochemical staining for 4 EMT-related proteins, namely E-cadherin, β-catenin, snail and vimentin, and two CSC-related proteins, namely CD44 and CD133, in two different tumor areas (the representative tumor center and the deepest invasive front) in 286 cases of primary CRC using tissue microarrays. Altered expression of all EMT-related proteins was more frequently observed in the invasive front than in the tumor center. Altered expression of E-cadherin, β-catenin and vimentin significantly associated with aggressive tumor characteristics. In particular, loss of E-cadherin expression in the invasive front significantly associated with shorter disease-free survival (DFS, P=0.002) and overall survival (OS, P=0.007). Overexpression of vimentin in the invasive front significantly correlated with poor OS (P=0.028). Loss of CD44 expression both in the tumor center and in the invasive front significantly associated with unfavorable clinicopathological characteristics. In the invasive front, but not in the tumor center, combination of the altered protein expression patterns of E-cadherin, β-catenin, vimentin, snail and CD133 significantly associated with aggressive clinicopathological factors and shorter DFS (P=0.003) and OS (P=0.005). The present data suggest that cancer cells expressing a combination of altered EMT- and CSC-related proteins may represent a potential biomarker for aggressive tumor behavior and may be a possible future candidate for molecular targeted treatments for CRC.

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