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Originally published online as doi:10.2353/ajpath.2009.081037 on May 14, 2009

Published online before print May 14, 2009
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(American Journal of Pathology. 2009;174:2347-2356.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.081037

Coordinate Expression of Colony-Stimulating Factor-1 and Colony-Stimulating Factor-1-Related Proteins Is Associated with Poor Prognosis in Gynecological and Nongynecological Leiomyosarcoma

Inigo Espinosa*, Andrew H. Beck*, Cheng-Han Lee{dagger}, Shirley Zhu*, Kelli D. Montgomery*, Robert J. Marinelli{ddagger}, Kristen N. Ganjoo§, Torsten O. Nielsen{dagger}, C. Blake Gilks{dagger}, Robert B. West* and Matt van de Rijn*

From the Departments of Pathology,* Biochemistry,{ddagger} and Clinical Oncology,§ Stanford University Medical Center, Stanford, California; and the Department of Pathology,{dagger} University of British Columbia, Vancouver, Canada

Previously, we showed that the presence of high numbers of macrophages correlates with poor prognosis in nongynecological leiomyosarcoma (LMS). In gynecological LMS, a similar trend was noted but did not reach statistical significance. Colony-stimulating factor-1 (CSF1) is a major chemoattractant for macrophages. Here we show that in a subset of LMS cases, CSF1 is expressed by the malignant cells. Previously, we found that CSF1 is translocated and highly expressed in tenosynovial giant cell tumors (TGCTs), and this observation allowed us to identify genes that showed a coordinate expression with CSF1. Here, we evaluated the expression of CSF1 and TGCT-associated proteins in 149 cases of LMS. The coordinate expression of CSF1 and three TGCT-associated proteins (CD163, FCGR3a, and CTSL1) identified cases with poor prognosis in both gynecological LMS (P = 0.00006) and nongynecological LMS (P = 0.03). In gynecological LMS, the coordinate expression of these four markers was the only independent prognosticator in multivariate analysis (hazard ratio, 4.2; 95% CI, 1.12 to 16; P = 0.03). Our findings indicate that CSF1 may play an important role in the clinical behavior of LMS that may open a window for new therapeutic reagents.






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