Stromal remodeling and SPARC (secreted protein acid rich in cysteine) expression in invasive ductal carcinomas of the breast

Virchows Arch. 2005 May;446(5):532-6. doi: 10.1007/s00428-005-1256-9. Epub 2005 Apr 19.

Abstract

In the present study, we analyzed tumor associated stromal remodeling with special respect to SPARC (secreted protein acid rich in cysteine) expression. 25 invasive ductal carcinomas of the breast and corresponding tumor-free breast tissue were studied immunohistochemically (CD34, alpha-SMA, SPARC and TGFbeta-R1). Tumor associated stroma was characterized by a loss of CD34 expression, paralleled by a gain in alpha-SMA. While SPARC expression was virtually absent from normal stromal cells in the tumor stroma, strong cytoplasmic SPARC reactivity was found in the majority of stromal cells. The TGFbeta-R1 also showed stronger expression in the tumor stroma compared to that of the normal breast. Stromal response to antecedent core needle biopsy was similar to that observed in the tumor stroma. We conclude that SPARC overexpression is a constant and functionally important feature of invasive ductal carcinomas, since SPARC mediates stromal de-adhesion crucial for local tumor invasion and systemic spread, respectively. When considering changes of the stromal phenotype (normal: CD34+alpha-SMA-SPARC- vs. carcinoma: CD34-alpha-SMA+SPARC+) as a tool in distinguishing benign from malignant breast lesion one has to keep in mind that the phenotype of granulation tissue in areas of antecedent biopsy resembles that of tumor stroma.

MeSH terms

  • Actins / analysis
  • Activin Receptors, Type I / analysis
  • Antigens, CD34 / analysis
  • Biopsy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology*
  • Female
  • Humans
  • Immunohistochemistry
  • Osteonectin / analysis*
  • Protein Serine-Threonine Kinases
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptors, Transforming Growth Factor beta / analysis
  • Stromal Cells / pathology*

Substances

  • Actins
  • Antigens, CD34
  • Osteonectin
  • Receptors, Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I