Published online before print June 4, 2009

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(American Journal of Pathology. 2009;175:334-341.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.081030

Prognostic Significance of Stromal Platelet-Derived Growth Factor β-Receptor Expression in Human Breast Cancer

Janna Paulsson^*, Tobias Sjöblom, Patrick Micke, Fredrik Pontén, Göran Landberg, Carl-Henrik Heldin, Jonas Bergh^*, Donal J. Brennan^¶, Karin Jirström and Arne Östman^*

From the Department of Oncology-Pathology,^* Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden; the Department of Genetics and Pathology, Uppsala University, Uppsala, Sweden; the Department of Laboratory Medicine, Division of Pathology, Lunds Universitet, Malmö, Sweden; the Ludwig Institute for Cancer Research, Uppsala, Sweden; and the UCD School of Biomolecular and Biomedical Science,^¶ UCD Conway Institute, University College, Dublin, Ireland

This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF β-receptor status and clinicopathological characteristics in breast cancer. PDGF receptor expression was determined by immunohistochemistry on tumor tissue microarrays. Breast tumor data were combined with prognostic factors and related to outcome endpoints. PDGF - and β-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF β-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF β-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF β-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF β-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF - and β-receptor expression is a common, but variable and independent, property of solid tumors. In breast cancer, stromal PDGF β-receptor expression significantly correlates with less favorable clinicopathological parameters and shorter survival. These findings highlight the prognostic significance of stromal markers and should be considered in ongoing clinical development of PDGF receptor inhibitors.

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