Expression of cancer stem cell markers in metastatic colorectal cancer correlates with liver metastasis, but not with metastasis to the central nervous system

Introduction: In colorectal cancer (CRC), metastatic spread is supposed to be mainly driven by tumor cells with stem cell features. Only about 1% of all CRC patients develop metastasis to the central nervous system (CNS). The present study intended to analyze the correlation between the expression of cancer stem cell markers and patterns of liver or CNS metastases. Material and methods: Immunohistochemistry for beta-catenin, CD133, CD44 and the mismatch-repair markers hMLH1 and hMSH2 was applied to primary specimen of two CRC cohorts with CNS (n= 29) and exclusive liver metastasis (n =36). Furthermore, mutation analysis for KRAS exon 2 and BRAF exon 15 was performed. Results: The expression of nuclear beta-catenin, CD44 and CD133 was associated with the development of liver metastasis, but not of CNS metastasis. CD133 expression was absent in CRC with solitary CNS metastasis. Combination of cancer stem cell markers revealed high discriminatory power for the prediction of different patterns of distant spread. KRAS mutation was more frequently detected in patients with CNS metastasis, but the mutational status of KRAS and BRAF failed to show correlation with clinico-pathological data or the results of immunohistochemistry. Conclusions: This study demonstrates that deregulation of Wnt/beta-catenin-signaling and high-grade expression of cancer stem cell markers correlate with metastasis to the liver, but not to the CNS. These data implicate that in CRC other mechanisms than deregulation of Wnt/beta-catenin-signaling and acquisition of cancer stemness are required for formation of CNS metastasis. (C) 2015 Elsevier GmbH. All rights reserved.