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Urol Oncol. 2014 Jul;32(5):678-86. doi: 10.1016/j.urolonc.2014.01.001. Epub 2014 Mar 12.

Expression and prognostic significance of cancer stem cell markers CD24 and CD44 in urothelial bladder cancer xenografts and patients undergoing radical cystectomy.

Author information

  • 1Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Urology, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: kontakt@thomashoefner.de.
  • 2Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany; Clinical Cooperation Unit Molecular Tumor Pathology, German Cancer Research Center, Heidelberg, Germany.
  • 3Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • 4Division of Stem Cells and Cancer, HI-STEM gGmbH, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: martin.sprick@hi-stem.de.

Abstract

OBJECTIVES:

To evaluate CD24/CD44/CD47 cancer stem cell marker expressions in bladder cancer (BCa) and provide data on their prognostic significance for clinical outcome in patients undergoing radical cystectomy (RC).

MATERIAL AND METHODS:

Primary BCa tissue was used for xenograft studies. A tissue microarray was prepared using specimens from a cohort of 132 patients. All patients underwent RC for urothelial BCa between 2001 and 2010. Expression of CD24, CD44, and CD47 was examined in primary samples and xenografts by fluorescence-activated cell sorting. Populations of CD24(low)- and CD24(high)-expressing cells were sorted and evaluated for tumorigenicity in vivo. Tissue microarray was analyzed for CD24/CD44 staining intensity and tumor-specific vs. stromal cell staining. Associations with BCa survival, BCa stage, and lymph node status were evaluated by univariate and multivariate analyses.

RESULTS:

CD24 and CD44/CD47 expressions mark distinct cell populations within the normal urothelium as well as in BCa. CD24(high/low) expression was not sufficient to characterize CD24 as a BCa-initiating marker in in vivo primary xenotransplants. CD24 and CD44 expressions correlated with lower cancer-specific survival in patients. However, multivariate analyses of CD24 or CD44 did not demonstrate significantly increased hazards for cancer-specific death if analyzed together with stage, grade, and nodal status of patients.

CONCLUSIONS:

Cancer stem cell markers CD24/CD44/CD47 are differentially expressed in cells of urothelial BCa in patients undergoing RC and influence cancer-specific survival of patients. Further evaluation of CD24/CD44/CD47 protein expression could be of high therapeutic value in BCa. However, both CD24 and CD44 expressions cannot be regarded as independent prognostic parameters for patients undergoing RC.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

Bladder cancer; CD24; CD44; CD47; Survival; Urothelial cancer

PMID:
24631171
[PubMed - indexed for MEDLINE]
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