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基质血小板衍生生长因子β受体表达在人类乳腺癌中的预后意义

Prognostic significance of stromal platelet-derived growth factor beta-receptor expression in human breast cancer.

作者信息

Paulsson Janna, Sjöblom Tobias, Micke Patrick, Pontén Fredrik, Landberg Göran, Heldin Carl-Henrik, Bergh Jonas, Brennan Donal J, Jirström Karin, Ostman Arne

机构信息

Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institutet, Stockholm, Sweden.

出版信息

Am J Pathol. 2009 Jul;175(1):334-41. doi: 10.2353/ajpath.2009.081030. Epub 2009 Jun 4.


DOI:10.2353/ajpath.2009.081030
PMID:19498003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2708819/
Abstract

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 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.

摘要

本研究系统分析了血小板衍生生长因子(PDGF)受体在六种常见肿瘤中的表达情况,并探讨了PDGFβ受体状态与乳腺癌临床病理特征之间的关联。通过免疫组织化学方法在肿瘤组织微阵列上测定PDGF受体的表达。将乳腺肿瘤数据与预后因素相结合,并与预后终点相关联。在所有测试的肿瘤类型的肿瘤基质中,PDGFα和β受体以不同频率独立表达。在个别结肠癌和前列腺癌中,成纤维细胞和血管周围细胞上的PDGFβ受体表达之间存在显著关联。在乳腺癌中,高基质PDGFβ受体表达与高组织病理学分级、雌激素受体阴性和高HER2表达显著相关。高基质PDGFβ受体表达与无复发生存期和乳腺癌特异性生存期显著缩短相关。基质PDGFβ受体表达的预后意义在绝经前女性的肿瘤中尤为突出。基质PDGFα和β受体表达是实体瘤的一种常见但可变且独立的特性。在乳腺癌中,基质PDGFβ受体表达与较差的临床病理参数和较短的生存期显著相关。这些发现突出了基质标志物的预后意义,在PDGF受体抑制剂的正在进行的临床开发中应予以考虑。

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[2]
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[5]
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[6]
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[9]
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[10]
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本文引用的文献

[1]
Low stroma androgen receptor level in normal and tumor prostate tissue is related to poor outcome in prostate cancer patients.

Prostate. 2009-6-1

[2]
A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer.

Nat Med. 2009-1

[3]
Paracrine signaling by platelet-derived growth factor-CC promotes tumor growth by recruitment of cancer-associated fibroblasts.

Cancer Res. 2009-1-1

[4]
Prognostic impact of platelet-derived growth factors in non-small cell lung cancer tumor and stromal cells.

J Thorac Oncol. 2008-9

[5]
Imatinib mesylate (Gleevec) in advanced breast cancer-expressing C-Kit or PDGFR-beta: clinical activity and biological correlations.

Ann Oncol. 2008-10

[6]
Stromal gene expression predicts clinical outcome in breast cancer.

Nat Med. 2008-5

[7]
Functions of paracrine PDGF signaling in the proangiogenic tumor stroma revealed by pharmacological targeting.

PLoS Med. 2008-1-29

[8]
Oestrogen receptors alpha and beta show different associations to clinicopathological parameters and their co-expression might predict a better response to endocrine treatment in breast cancer.

J Clin Pathol. 2008-2

[9]
Platelet-derived growth factor receptor expression and amplification in choroid plexus carcinomas.

Mod Pathol. 2008-3

[10]
Breast-cancer stromal cells with TP53 mutations and nodal metastases.

N Engl J Med. 2007-12-20

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