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Prognostic Significance of CD44v6, CD133, CD166, and ALDH1 Expression in Small Intestinal Adenocarcinoma

Eom, Dae-Woon MD, PhD*; Hong, Seung-Mo MD, PhD; Kim, Gwangil MD, PhD; Bae, Young Kyung MD, PhD§; Jang, Kee-Taek MD, PhD; Yu, Eunsil MD, PhD

Applied Immunohistochemistry & Molecular Morphology: November/December 2015 - Volume 23 - Issue 10 - p 682–688
doi: 10.1097/PAI.0000000000000140
Research Articles

Background: Small intestinal adenocarcinoma (SIAC) is a rare human malignant tumor. According to the cancer stem cell (CSC) hypothesis, only a small subpopulation of tumor cells has the ability to initiate and increase tumor growth. CD44v6, CD133, CD166, and ALDH1 have been proposed to be putative CSC markers in gastrointestinal malignancies. However, their implications in SIAC still remain unclear. We aimed to investigate the expressions of CD44v6, CD133, CD166, and ALDH1 and evaluate their relationships with clinicopathologic parameters including the survival data in SIACs.

Materials and Methods: Immunohistochemical analysis for CD44, CD133, CD166, and ALDH1 was performed using tissue microarrays for 191 surgically resected SIACs.

Results: CD44v6, CD133, CD166, and ALDH1 expression was found in 25 (13.5%), 58 (30.7%), 82 (44.1%), and 63 (33.3%) cases, respectively. CD44v6+ was correlated with vascular tumor invasion (P=0.023). CD133+ was marginally correlated with the histologic subtype of the tumors (P=0.085). Combined CD44v6+/CD133+ was observed in 11 (5.9%) and was associated with a significantly worse survival rate by univariate (P=0.016) and multivariate (P=0.048; Cox hazard ratio, 2.403) analyses.

Conclusions: Evaluation of the combined CD133 and CD44v6 expression could be a useful tool for predicting a poor outcome in patients with SIAC.

*Department of Pathology, Gangneung Asan Hospital

Asan Medical Center, University of Ulsan College of Medicine

Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul

Bundang CHA Medical Center, CHA University, Seongnam

§Yeungnam University College of Medicine, Daegu, Korea

Funded by the Gangneung Asan Hospital Biomedical Research Center Promotion Fund & Basic Science Research Program through the National Research Foundation of Korea (NRF) by the Ministry of Education, Science and Technology (2010-0004807).

The authors declare no conflict of interest.

Reprints: Dae-Woon Eom, MD, PhD, Department of Pathology, University of Ulsan College of Medicine, Gangneung Asan Hospital, 415, Bangdong-ri, Sacheon-myeon, Gangneung-si, Gangwon-do 210-711, Korea (e-mail:

Received December 4, 2013

Accepted August 15, 2014

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