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. Global gene expression profiling data of a series of soft tissue tumors were analyzed for macrophage-associated gene expression. Immunohistochemistry on tissue microarrays containing leiomyosarcoma 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, 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 leiomyosarcomas. 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 nongynecologic leiomyosarcomas, whereas leiomyosarcomas 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- or CD68-positive tumor-infiltrating macrophages is associated with poor outcome in nongynecologic leiomyosarcomas. This may help the clinical management of patients with leiomyosarcomas.
Highlights
Macrophages are migratory cells that are frequently recruited to the site of tumors
We found that the density of intratumoral CD68- or CD163-positive macrophages in primary leiomyosarcomas arising outside of the gynecologic tract locations is inversely correlated with patient outcome
Kaplan-Meier survival analysis of the nongynecologic leiomyosarcomas based on the FNCLCC grading system showed a trend toward poorer outcome with higher grade, which did not reach statistical significance (P = 0.17; Supplementary Fig. S3). These results showed that higher density of macrophage infiltration as shown by CD68 immunostaining and, in particular, by CD163 immunostaining is a negative predictor of patient survival in nongynecologic leiomyosarcomas, and this significant association with survival is not related to the presence of tumor necrosis
Summary
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. Results: Gene expression profiling revealed high-level expression of several macrophageassociated genes such as CD163 and CD68 in a subset of leiomyosarcomas, 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 leiomyosarcomas. Conclusions: An increased density of CD163- or CD68-positive tumor-infiltrating macrophages is associated with poor outcome in nongynecologic leiomyosarcomas This may help the clinical management of patients with leiomyosarcomas. In the present study, using gene expression profiling, we observed high-level expression of a number of macrophageassociated genes in a subset of leiomyosarcomas and subsequently examined the prognostic significance of tumor-infiltrating macrophages as identified by CD68 or CD163 immunostains on tissue microarrays. We found that the density of intratumoral CD68- or CD163-positive macrophages in primary leiomyosarcomas arising outside of the gynecologic tract locations is inversely correlated with patient outcome
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