Association of stem cell marker expression pattern and survival in human biliary tract cancer

Kemmerling,Ralf; Alinger,Beate; Dietze,Otto; Bösmüller,Hans-Christian; Ocker,Matthias; Wolkersdörfer,Gernot  W.; Berr,Frieder; Neureiter,Daniel; Kiesslich,Tobias

doi:10.3892/ijo.2012.1477

Association of stem cell marker expression pattern and survival in human biliary tract cancer

Authors:
- Ralf Kemmerling
- Beate Alinger
- Otto Dietze
- Hans-Christian Bösmüller
- Matthias Ocker
- Gernot W. Wolkersdörfer
- Frieder Berr
- Daniel Neureiter
- Tobias Kiesslich
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Affiliations: Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria, Institute of Pathology, Krankenhaus Barmherzige Schwestern Linz, 4020 Linz, Austria, Institute for Surgical Research, Philipps-University Marburg, 35043 Marburg, Germany, Department of Internal Medicine I, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria
Published online on: May 14, 2012 https://doi.org/10.3892/ijo.2012.1477
Pages: 511-522

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Abstract

The aim of this study was to investigate the molecular and protein expression pattern of markers of stemness phenotype and its clinicopathological significance in human biliary tract cancer (BTC). Human BTC cell lines (CCLP-1, Egi-1, MzChA-1, MzChA-2, SkChA-1, TFK-1 and GBC) were analyzed in vitro and in xenotransplanted animals for expression of markers of stemness and compared to tissue microarrays (TMA) of 34 cases of human BTC with complete pathomorphological and clinical data (survival). Molecular analyses on the mRNA and protein level included makers of stemness and progenitor (Bmi-1, Sox-2, Nestin, CD133, CD44 and Nanog), proliferation and differentiation (cell cycle proteins, intermediate filaments). The investigated BTC samples showed a low to moderate and partially significantly different expression pattern of the stem cell markers in vitro, in vivo and in TMA. Hierarchical cluster analysis identified subgroups with homogenous expression of stem cell markers significantly differing with respect to cytokeratin expression in xenografts and Ki67 proliferation marker in human TMA, respectively - thus indicating possible heterogeneous carcinogenesis pathways in BTC. Additionally, these stem cell markers could be linked to morphology and molecular markers of proliferation and differentiation on the mRNA and protein level. Finally, survival analysis identified the combination of CD133 and CD44 as an independent prognostic factor yet their value as prognostic factors need testing in prospective study design.

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