Elsevier

Modern Pathology

Volume 23, Issue 3, March 2010, Pages 450-457
Modern Pathology

Article
CD133 expression predicts for non-response to chemotherapy in colorectal cancer

https://doi.org/10.1038/modpathol.2009.181Get rights and content
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Abstract

The cancer stem cell hypothesis may explain why conventional chemotherapies are unable to fully eradicate cancers. In this study, we examined both the prognostic and predictive significance of putative cancer stem cell markers in colorectal cancer. In this study, immunohistochemistry for three candidate cancer stem cell markers (CD133, Oct-4 and Sox-2) and for six other postulated prognostic markers (CK7, CK20, Cox-2, Ki-67, p27 and p53) were performed using tissue microarrays containing 501 primary colorectal cancer cases. Receiver-operating characteristic analysis was used to determine cut-off scores for positive protein expression. Multivariate analysis revealed that positive expression for CD133 and Oct-4 was associated with significantly worse survival in patients treated by surgery alone (P=0.023 and P<0.001, respectively) and in patients treated with 5-fluorouracil-based chemotherapy (P=0.001 and P=0.021, respectively). Stage III patients with negative CD133 expression showed an apparent survival benefit from 5-fluorouracil treatment (P=0.002), but not those with positive CD133 expression. Positive expression of CD133 was also associated with poorer clinical response to chemotherapy in stage IV patients (P=0.006). In summary, the putative cancer stem cell markers CD133 and Oct-4 showed strong prognostic significance in colorectal cancer. Our results show for the first time that CD133+ colorectal tumors are more resistant to 5-fluorouracil-based chemotherapy.

CD133
colorectal cancer
cancer stem cell
prognosis
chemoresistance

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Supplementary information The online version of this article (doi:10.1038/modpathol.2009.181) contains supplementary material, which is available to authorized users.

Disclosure/conflict of interest

The authors declare no conflict of interest.

Supplementary Information accompanies the paper on Modern Pathology website (http://www.nature.com/modpathol)