Elevated expression of the tyrosine phosphatase SHP-1 defines a subset of high-grade breast tumors

Oncology. 2009;77(6):378-84. doi: 10.1159/000276765. Epub 2010 Jan 18.

Abstract

Objectives: Protein tyrosine phosphatases are key regulators of intracellular signaling that contribute to determining cancer cell growth, which thus makes them attractive targets for therapeutic and diagnostic agents. SHP-1 phosphotyrosine phosphatase is rarely expressed in epithelial tumor cells, but expression has been found in several breast cancer cell lines and tumors. To determine the potential significance of SHP-1 as a prognostic marker in the clinical setting, we examined SHP-1 protein expression in breast tumors.

Methods: We analyzed SHP-1 expression by immunohistochemistry in a breast tissue microarray composed of 2,081 cores, either alone or in combination with known prognostic markers.

Results: Our data showed that SHP-1 expression was confined to a well-defined subset of high-grade tumors characterized by unique biological parameters. SHP-1 expression correlated directly with expression of the tyrosine kinase receptor HER-2 and inversely with expression of the estrogen receptor, while it was weakly associated with Bcl-2 expression.

Conclusions: Levels of SHP-1 were correlated with conventional pathologic parameters of tumor aggressiveness and were associated with reduced patient survival, suggesting that elevated expression of SHP-1 is a common molecular abnormality in a defined subset of breast tumors and might be used in routine diagnosis to identify patients with high-risk tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinase Inhibitor p16 / analysis
  • Female
  • Genes, bcl-2
  • Humans
  • Immunohistochemistry
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6 / analysis*

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6