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Chondroitin sulfate expression predicts poor outcome in breast cancer.

Svensson, Katrin LU ; Christianson, Helena LU ; Kucharzewska, Paulina LU ; Fagerström, Victor; Lundstedt, Lars; Borgquist, Signe LU ; Jirström, Karin LU and Belting, Mattias LU (2011) In International Journal of Oncology 39. p.1421-1428
Abstract
Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess... (More)
Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between chondroitin sulfate and recurrence-free and overall survival. High chondroitin sulfate expression in malignant cells was shown to predict shorter recurrence-free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival (cohort I: P=0.044; cohort II: P<0.001) in both cohorts. In multivariate analysis, high chondroitin sulfate in malignant cells was shown to be an independent, predictive factor of poor overall survival (cohort I: hazard ratio 2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71: 95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the stroma showed no correlation with known markers of tumor aggressiveness or with clinical outcome in either cohort. Our data suggest that high chondroitin sulfate expression in malignant cells is associated with an adverse outcome in patients with primary breast cancer, supporting the idea of a functional and potentially targetable role of chondroitin sulfate in tumor disease. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
International Journal of Oncology
volume
39
pages
1421 - 1428
publisher
D.A. Spandidos
external identifiers
  • wos:000296315400010
  • pmid:21850370
  • scopus:80054804895
ISSN
1019-6439
DOI
10.3892/ijo.2011.1164
language
English
LU publication?
yes
id
16cbd9b7-3739-4889-97c4-2e2c28390bac (old id 2150878)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21850370?dopt=Abstract
date added to LUP
2011-09-04 13:55:07
date last changed
2017-10-22 04:59:03
@article{16cbd9b7-3739-4889-97c4-2e2c28390bac,
  abstract     = {Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between chondroitin sulfate and recurrence-free and overall survival. High chondroitin sulfate expression in malignant cells was shown to predict shorter recurrence-free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival (cohort I: P=0.044; cohort II: P&lt;0.001) in both cohorts. In multivariate analysis, high chondroitin sulfate in malignant cells was shown to be an independent, predictive factor of poor overall survival (cohort I: hazard ratio 2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71: 95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the stroma showed no correlation with known markers of tumor aggressiveness or with clinical outcome in either cohort. Our data suggest that high chondroitin sulfate expression in malignant cells is associated with an adverse outcome in patients with primary breast cancer, supporting the idea of a functional and potentially targetable role of chondroitin sulfate in tumor disease.},
  author       = {Svensson, Katrin and Christianson, Helena and Kucharzewska, Paulina and Fagerström, Victor and Lundstedt, Lars and Borgquist, Signe and Jirström, Karin and Belting, Mattias},
  issn         = {1019-6439},
  language     = {eng},
  pages        = {1421--1428},
  publisher    = {D.A. Spandidos},
  series       = {International Journal of Oncology},
  title        = {Chondroitin sulfate expression predicts poor outcome in breast cancer.},
  url          = {http://dx.doi.org/10.3892/ijo.2011.1164},
  volume       = {39},
  year         = {2011},
}