Prognostic significance of macrophage infiltration in leiomyosarcomas.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


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.
Lee
Cheng-Han
CH
Department of Pathology, Stanford University Medical Center, Stanford, California 94305, USA.
Espinosa
Inigo
I
Vrijaldenhoven
Suzan
S
Subramanian
Subbaya
S
Montgomery
Kelli D
KD
Zhu
Shirley
S
Marinelli
Robert J
RJ
Peterse
Johannes L
JL
Poulin
Neal
N
Nielsen
Torsten O
TO
West
Rob B
RB
Gilks
C Blake
CB
van de Rijn
Matt
M
D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D007890:Leiomyosarcoma / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000235:genetics*; D012983:Soft Tissue Neoplasms / Q000473:pathology*; D015996:Survival Rate; D046888:Tissue Array Analysis; D000098902:CD163 Antigen; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D014408:Biomarkers, Tumor; D011956:Receptors, Cell Surface; D000098902:CD163 Antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule