CSF1-Response Signature Is Associated with Tumor Angiogenesis in Non-Gynecological Leiomyosarcoma.
Inigo Espinosa, Andrew Beck, Badreddin Edris, Cheng-Han Lee, Robert West, Matt van de Rijn. Stanford University School of Medicine, CA; Universidad Autònoma de Barcelona, Spain; University of British Columbia, Vancouver, Canada
Background: Both Colony-Stimulating Factor-1 (CSF1) expression by tumor cells and stromal macrophage infiltration are associated with poor prognosis in leiomyosarcoma (LMS) but the mechanisms underlying these observed prognostic associations are not well understood. While it has been shown that in carcinomas, tumor-associated macrophages (TAMs) have been found to promote tumor angiogenesis, no such relationship has been exhibited in LMS.
Design: We analyzed the relationship between genes we previously identified to correlate with macrophage-rich inflammatory infiltration in tumor sites (“CSF1 Signature”) with genes that play key roles in angiogenesis; this analysis was carried out in a series of LMS cases for which we had gene expression profiling data. We subsequently examined the density of CD34-positive microvessels in relation to CSF1 expression, VEGFC expression, macrophage density, and patient outcome in a series of 76 gynecologic and 73 non-gynecologic primary LMS.
Results: VEGFC and vascular markers like CD34 were found to be positively associated with the CSF1 Signature in non-gynecologic LMS. VEGFA and VEGFB showed no association with CSF1 levels. On average, gynecologic LMS showed greater microvessel density (35/0.6mm) than non-gynecologic LMS (22/0.6mm) (P<0.05). For non-gynecologic LMS, microvessel density correlated with CSF1 expression, macrophage density, and VEGFC expression (all with P<0.05). The presence of increased microvessel density was associated with decreased disease-specific survival by Kaplan-Meier analysis (P=0.004), while no correlation was found between vessel density and VEGFC levels. There was no significant correlation between microvessel density and patient survival in gynecologic LMS. The patterns of CSF1 expression, macrophage recruitment and microvessel density were well maintained between primary-metastatic tumor pairs indicating that these features are intrinsic to the biology of LMS
Conclusions: These findings link increased microvessel formation to tumoral CSF1 expression and stromal macrophage infiltration and suggest enhanced tumor angiogenesis as a mechanism utilized by CSF1-recuited/activated stromal macrophages to aid the progression of non-gynecologic LMS.
Category: Bone & Soft Tissue
Monday, February 28, 2011 1:00 PM
Poster Session II # 13, Monday Afternoon