Differing Prognostic Significance of Tumor Associated Macrophages in Gastrointestinal Leiomyosarcomas and Gastrointestinal Stromal Tumors
CH Lee, SE Steigen, I Espinosa, LF Lopes, CE Bacchi, CB Gilks, TO Nielsen, M van de Rijn. Vancouver General Hospital, Vancouver, BC, Canada; Institute of Medical Biology, University of Tromsø, Tromsø, Norway; Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain; Consultoria em Patologia, Botucatu, SP, Brazil; Stanford University Medical Center, Stanford, CA
Background: Gastrointestinal stromal tumors (GIST) and leiomyosarcomas (LMS) are two mesenchymal tumors that can arise anywhere along the gastrointestinal tract. While they were initially thought to represent the same disease, it is now clear that they are biologically distinct entities. We have previously demonstrated the prognostic significance of tumor associated macrophages in a series of predominantly soft tissue based LMS. The extent and the importance of stromal macrophage infiltrate in GIST and gastrointestinal LMS however remains uncharacterized.
Design: Using a series of tissue microarrays that contain 419 GIST and 63 gastrointestinal LMS with long term follow-up, we determined the density of the macrophages in each 0.6 mm tumor cores with the macrophage marker CD163 and examined its prognostic significance by Kaplan-Meier analysis.
Results: CD163-positive stromal macrophages were present in nearly all GIST and all gastrointestinal LMS examined. While macrophage density varied between tumors, LMS overall showed greater amount of macrophages in their stroma (median density of 45 macrophages per core) when compared to GIST (median density of 21 macrophages per core). Kaplan-Meier survival analysis showed no significant differences between subgroups of GIST with different macrophage densities. In contrast, dense stromal macrophage infiltrates (> 70 macrophages per core) in gastrointestinal LMS was associated with decreased 5-year overall survival (20% versus 55%, p=0.009) with the difference being significant up to 20-year follow-up (p=0.011). Presence of tumor necrosis was found to be a significant negative prognosticator for GIST (p=0.008) but not for gastrointestinal LMS (p=0.512).
Conclusions: We have observed a significant association between dense stromal macrophage infiltrates and decreased overall survival in gastrointestinal LMS but not in GIST. This finding likely reflects known differences in the biology between them. It also provides further support to the importance of tumor associated macrophages in the progression of LMS, irrespective of the site of origin.
Category: Bone & Soft Tissue
Monday, March 22, 2010 1:00 PM
Poster Session II # 24, Monday Afternoon