Thrombospondin-1 and -2 in node-negative breast cancer: Correlation with angiogenic factors, p53, cathepsin D, hormone receptors and prognosis

Giampietro Gasparini, Masakazu Toi, Elia Biganzoli, Ruggero Dittadi, Massimo Fanelli, Alessandro Morabito, Patrizia Boracchi, Massimo Gion

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Abstract

Objective: Thrombospondins (TSPs) are a multigene family of five secreted glycoproteins involved in the regulation of cell proliferation, adhesion and migration. Two members of the TSP family, namely TSP-1 and TSP-2, are also naturally occurring inhibitors of angiogenesis. The aim of the present study was to determine the prognostic significance of the determination of TSP-1 and -2 and their correlation with the angiogenic peptides vascular endothelial growth factor (VEGF) and thymidine phosphorylase (TP), as well as with other biological and clinicopathological features investigated. Methods: We evaluated a series of 168 women with node-negative breast cancer with a median follow-up period of 66 months, not treated with adjuvant therapy. The cytosolic levels of TSP-1 and -2 were determined in the primary tumour by a commercially available immunometric assay. Results: We found that 166 tested tumours had measurable levels of TSP-1 and -2 protein (median value 5.978, range 0.579-31.410 ng/mg of protein). On the basis of Spearman's rank correlation coefficient, a weak inverse association of TSP-1 and -2 with tumour size and cathepsin D was found. Moreover, principal component analysis on ranks evidenced a poor association between TSP-1 and -2, VEGF and TP. The results of the clinical outcome were analysed by both univariate and multivariate [for relapse-free survival (RFS) only]) Cox regression models. TSP-1 and -2 were not significant prognostic factors in univariate analysis for either RFS (p = 0.427) or overall survival (p = 0.069). To investigate the 'angiogenic balance hypothesis', bivariate analyses were performed to investigate the interactions of TSP-1 and -2 with VEGF, TP or p53, but none were included in the selected models. Finally, in multivariate analysis for RFS a baseline model, previously defined in a larger case series and inclusive of VEGF, TP and their interaction was adopted. It was highly significant (p = 0.002, Harrell c statistic value of 0.703); but when TSP-1 and -2 were added, their contribution was negligible (p = 0.731, Harrell c statistic value of 0.705). Conclusions: The results of this study suggest that TSP-1 and -2 do not provide additional prognostic contribution to the joint effects of VEGF and TP. In the series of node-negative breast cancer patients investigated, determination of the angiogenic peptides VEGF and TP gave significant prognostic information. On the contrary, TSP-1 and -2, potential naturally occurring negative regulators of angiogenesis, lacked of prognostic value.

Original languageEnglish
Pages (from-to)72-80
Number of pages9
JournalOncology
Volume60
Issue number1
DOIs
Publication statusPublished - 2001

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Keywords

  • Breast cancer
  • Prognosis
  • Thrombospondin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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