The macrophage colony-stimulating factor 1 response signature in breast carcinoma.
OBJECTIVE
Macrophages play an important role in breast carcinogenesis. The pathways that mediate the macrophage contribution to breast cancer and the heterogeneity that exists within macrophages are incompletely understood. Macrophage colony-stimulating factor 1 (CSF1) is the primary regulator of tissue macrophages. The purpose of this study was to define a novel CSF1 response signature and to evaluate its clinical and biological significance in breast cancer.


METHODS
We defined the CSF1 response signature by identifying genes overexpressed in tenosynovial giant cell tumor and pigmented villonodular synovitis (tumors composed predominantly of macrophages recruited in response to the overexpression of CSF1) compared with desmoid-type fibromatosis and solitary fibrous tumor. To characterize the CSF1 response signature in breast cancer, we analyzed the expression of CSF1 response signature genes in eight published breast cancer gene expression data sets (n = 982) and did immunohistochemistry and in situ hybridization for CSF1 response genes on a breast cancer tissue microarray (n = 283).


RESULTS
In both the gene microarray and tissue microarray analyses, a consistent subset (17-25%) of breast cancers shows the CSF1 response signature. The signature is associated with higher tumor grade, decreased expression of estrogen receptor, decreased expression of progesterone receptor, and increased TP53 mutations (P < 0.001).


CONCLUSIONS
Our data show that the CSF1 response signature is consistently seen in a subset of breast carcinomas and correlates with biological features of the tumor. Our findings provide insight into macrophage biology and may facilitate the development of personalized therapy for patients most likely to benefit from CSF1-targeted treatments.
Beck
Andrew H
AH
Department of Pathology, Stanford University Medical Center, Stanford, California 94305, USA.
Espinosa
Inigo
I
Edris
Badreddin
B
Li
Rui
R
Montgomery
Kelli
K
Zhu
Shirley
S
Varma
Sushama
S
Marinelli
Robert J
RJ
van de Rijn
Matt
M
West
Robert B
RB
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality; D019992:Databases as Topic; D015870:Gene Expression; D006801:Humans; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics*; D017154:Stromal Cells / Q000378:metabolism; D016019:Survival Analysis
D016173:Macrophage Colony-Stimulating Factor