gms | German Medical Science

128. Kongress der Deutschen Gesellschaft für Chirurgie

Deutsche Gesellschaft für Chirurgie

03.05. - 06.05.2011, München

Detection of disseminated tumor initiating cells in patients with colorectal cancer – which marker is of clinical relevance?

Meeting Abstract

  • Mia Kim - Universtitätsklinikum Würzburg, Chirurgie I, Würzburg
  • Tanja Grimmig - Universtitätsklinikum Würzburg, Chirurgie I , Molekulare Onkoimmunologie, Würzburg
  • Markus Frank - Harvard Medical School, Children's and Brigham's Hospital, Boston
  • Natasha Frank - Harvard Medical School, Children's and Brigham's Hospital, Boston
  • Christoph-Thomas Germer - Universtitätsklinikum Würzburg, Klinik und Poliklinik für Allgemein- und Viszeralchirurgie, Würzburg
  • Ana Maria Waaga-Gasser - Universtitätsklinikum Würzburg, Chirurgie I , Molekulare Onkoimmunologie, Würzburg
  • Martin Gasser - Universtitätsklinikum Würzburg, Chirurgie I, Würzburg

Deutsche Gesellschaft für Chirurgie. 128. Kongress der Deutschen Gesellschaft für Chirurgie. München, 03.-06.05.2011. Düsseldorf: German Medical Science GMS Publishing House; 2011. Doc11dgch340

DOI: 10.3205/11dgch340, URN: urn:nbn:de:0183-11dgch3401

Published: May 20, 2011

© 2011 Kim et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.en). You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.


Outline

Text

Introduction: Spreading of differentiated tumor cells and tumor initiating cells (TICs) from primary tumors into the periphery may occur early during tumor progression. However, TICs could be mainly responsible for tumor relapses and metachronic metastases. This study evaluates ABCB5, a newly defined surface marker, Lgr5 as Wnt target gene and CD133 as putative markers for TICs compared with CK20, a marker for disseminated tumor cells, in preoperatively obtained blood samples from patients with colorectal cancer (CRC).

Materials and methods: Peripheral blood from 105 patients with CRC (UICC stages I to III) and completed 5-year follow up was analyzed by RT-PCR for ABCB5, Lgr5 and CD133 as well as CK20. Gene expression results were compared to a cohort of 19 healthy individuals. For statistical analysis Mann-Whitney U-Test, Fisher’s respectively Chi Quadrat-Test and Correlation of Pearson were used. For overall survival and cumulative relapse probability Kaplan-Meier analysis and Log Rank-Test were performed.

Results: ABCB5 and CD133 but not Lgr5 expression was significantly upregulated in patients with CRC compared to controls (p<0.001 respectively). There was no significant difference for marker positive and negative samples concerning age, gender, tumor differentiation, T- and N-category, UICC-stage and CK20 positivity. Only patients with upregulated CD133 gene expression in qPCR showed a UICC-stage dependency (p=0.02). However, there was a significant correlation of upregulated expression levels between all markers (p=0.0001 respectively). Neither overall survival nor cumulative relapse probability were influenced by upregulated marker expression. In contrast, expression of CK20 did influence overall survival (p=0.03).

Conclusion: Upregulated gene expression of ABCB5, Lgr5 and CD133 in peripheral blood represents an early event in carcinogenesis and initial tumor progression. It may reflect spreading of TICs which could be responsible even for late tumor relapses. Other factors than mRNA expression of tumor-initiating cells in the peripheral blood may additionally contribute to relapse probability and overall survival.