Histological Images

Supplementary Data



The Macrophage Colony Stimulating Factor-1 Response Signature in Breast Carcinoma

Andrew H Beck*1, Inigo Espinosa*1, Badreddin Edris1, Rui Li1, Kelli Montgomery1, Shirley Zhu1, Sushama Varma1, Robert J Marinelli2, Matt van de Rijn1, Robert B West1,3

Welcome to the web supplement, where you may view all stained histological images, figures and supplementary data for The Macrophage Colony Stimulating Factor-1 Response Signature in Breast Carcinoma.

Clinical Cancer Research 15, 778-787, February 1, 2009. doi: 10.1158/1078-0432.CCR-08-1283


Macrophages play an important role in breast carcinogenesis. The pathways that mediate the macrophage contribution to breast cancer and the heterogeneity that may exist 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.

Experimental Design:
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) as 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 datasets (n=982) and performed immunohistochemistry and in situ hybridization for CSF1 response genes on a breast cancer tissue microarray (n=283).

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 p53 mutations (p <0.001).

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.

1Department of Pathology, Stanford University Medical Center, Stanford, California, United States of America.

2Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.

3Pathology and Laboratory Service, Palo Alto Veterans Affairs Health Care System, Palo Alto, CA, United States of America.

* These authors contributed equally to this work.