Prognostic significance of macrophage infiltration in leiomyosarcomas

 Cheng-Han Lee1, 2 †, Inigo Espinosa1†, SuzanVrijaldenhoven1,

Subbaya Subramanian1,Kelli D Montgomery1, Shirley Zhu1, Robert J Marinelli3, Johannes L Peterse 4, Neal Poulin2, Torsten O. Nielsen2, Rob B. West1,

C. Blake Gilks2, Matt van de Rijn1.

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Welcome to the web supplement for the paper Prognostic significance of macrophage infiltration in leiomyosarcomas Clinical Cancer Research 14, 1423-1430, March 1, 2008. doi: 10.1158/1078-0432.CCR-07-1712

  • Abstract


    Macrophages are migratory cells that are frequently recruited to the site of tumors.  Their presence is associated with poor clinical outcome in a variety of epithelial malignancies.  The aim of this study is to examine the prognostic significance of tumor associated macrophages in sarcomas. 

    Experimental Design

    Global gene expression profiling data of a series of soft tissue tumors was analyzed for macrophage-associated gene expression.  Immunohistochemistry on tissue microarrays containing LMS cases with known clinical outcome was used to verify the presence of macrophages and to examine the relationship between tumor-associated macrophages and clinical outcome. 


    Gene expression profiling revealed high-level expression of several macrophage associated genes such as CD163 and CD68 in a subset of leiomyosarcomas (LMS), indicating the presence of variable numbers of tumor infiltrating macrophages. This was confirmed by CD68 and CD163 immunostaining of a tissue microarray containing 149 primary LMS.  Kaplan-Meier survival analysis showed that high density of tumor infiltrating macrophages as identified by CD163 or CD68 staining is associated with a significantly worse disease specific survival in non-gynecologic LMS whereas LMS arising from the gynecologic tract showed no significant association between macrophage infiltration and survival.   The presence of tumor necrosis did not correlate significantly with outcome. 


    An increased density of CD163 positive or CD68 positive tumor infiltrating macrophages is associated with poor outcome in non-gynecologic LMS.  This may help the clinical management of patients with LMS.

    1 Department of Pathology, Stanford University Medical Center, 300 Pasteur Drive, Stanford, CA, USA, 94305; 2 Department of Anatomical Pathology, Vancouver General Hospital, 920 West 10th Avenue, Vancouver, British Columbia, Canada, V5Z 1M9; 3 Department of Biochemistry, Stanford University Medical Center,  4Department of Diagnostic Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.