title: Expression of cancer stem cell markers in metastatic colorectal cancer correlates with liver metastasis, but not with metastasis to the central nervous system.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Immunohistochemistry for β-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 β-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/β-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/β-catenin-signaling and acquisition of cancer stemness are required for formation of CNS metastasis.
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Marlies
authors.initials: M
authors.lastname: Michl
authors.affiliation: Department of Medical Oncology, Klinikum Grosshadern and Comprehensive Cancer Center, Ludwig-Maximilians-Universität München, Munich, Germany; German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Heinemann
authors.affiliation: German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jung
authors.affiliation: Munich Cancer Registry (MCR), Klinikum Grosshadern, Ludwig-Maximilians-Universität München, Munich, Germany; Institute of Medical Informatics, Biometry and Epidemiology (IBE), Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Engel
authors.affiliation: German Cancer Consortium (DKTK), 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany; Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany. Electronic address: jens.neumann@med.uni-muenchen.de.
authors.forename: Jens
authors.initials: J
authors.lastname: Neumann
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000032:analysis*; D016543:Central Nervous System Neoplasms / Q000378:metabolism / Q000556:secondary; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000473:pathology*
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor
keywords: Brain metastasis; CD133; CD44; Colorectal cancer; Liver metastasis; β-Catenin