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

被引:198
作者
Paulsson, Janna [1 ]
Sjoblom, Tobias [2 ]
Micke, Patrick [2 ]
Ponten, Fredrik [2 ]
Landberg, Goran [3 ]
Heldin, Carl-Henrik [4 ]
Bergh, Jonas [1 ]
Brennan, Donal J. [5 ]
Jirstrom, Karin [3 ]
Ostman, Arne [1 ]
机构
[1] Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, S-17176 Stockholm, Sweden
[2] Uppsala Univ, Dept Genet & Pathol, Uppsala, Sweden
[3] Lund Univ, Dept Lab Med, Div Pathol, Malmo, Sweden
[4] Ludwig Inst Canc Res, S-75124 Uppsala, Sweden
[5] Univ Coll Dublin, UCD Conway Inst, UCD Sch Biomol & Biomed Sci, Dublin 2, Ireland
基金
瑞典研究理事会;
关键词
TUMOR STROMA; PERICYTE RECRUITMENT; IMATINIB MESYLATE; CELL-GROWTH; PDGFR-ALPHA; B-CHAIN; INHIBITION; CARCINOMA; TISSUE; GENE;
D O I
10.2353/ajpath.2009.081030
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
This study systematically analyzes platelet-derived growth factor (PDGF) receptor expression in six types of common tumors as well as examines associations between PDGF beta-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 alpha- and beta-receptors were independently expressed, at variable frequencies, in the tumor stroma of all tested tumor types. There was a significant association between PDGF beta-receptor expression on fibroblasts and perivascular cells in individual colon and prostate tumors. In breast cancer, high stromal PDGF beta-receptor expression was significantly associated with high histopathological grade, estrogen receptor negativity, and high HER2 expression. High stromal PDGF beta-receptor expression was correlated with significantly shorter recurrence-free and breast cancer-specific survival. The prognostic significance of stromal PDGF beta-receptor expression was particularly prominent in tumors from premenopausal women. Stromal PDGF alpha- and beta-receptor expression is a common, but variable and independent, property of solid tumors. in breast cancer, stromal PDGF beta-receptor expression significantly correlates with less favorable clinicopatho-logical 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. (Am J Pathol 2009, 175.334-341; DOI: 10.2353/ajpath.2009.081030)
引用
收藏
页码:334 / 341
页数:8
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