Differing Prognostic Associations of Tumor Stromal Macrophages in Different Molecular Subtypes of Breast Cancers
Anna F Lee, Hassan Huwait, Sam Leung, Jennifer Choo, Torsten O Nielsen, Cheng-Han Lee. Univ. of British Columbia, Vancouver, BC, Canada; Vancouver Gen. Hosp., Vancouver, BC, Canada
Background: Dense stromal macrophage infiltrates are associated with poor prognosis in breast cancer as a group overall. Experiments in some breast cancer models have implicated tumor-macrophage interactions in cancer progression. Although genetic differences between the different molecular subtypes of breast cancer is well established, the prognostic significance of tumor associated macrophages in the different subtypes remains poorly understood.
Design: We performed a study on a series of 166 breast cancers with clinical follow-up data. Individual cases were represented by duplicate tumor cores on a tissue microarray. These cases were immunohistochemically subtyped (Cheang et al. Journal of National Cancer Institute. 2009;101:736-50, and Clinical Cancer Research. 2008;14:1368-76) and a total of 93 luminal type A, 51 luminal type B, and 22 basal type cases were represented. The number of stromal macrophages highlighted by CD163 immunostaining (Novocastra) was manually quantified, without knowledge of subtype, and normalized to the tissue core area for determination of macrophage density. Kaplan-Meier survival and univariable Cox regression analyses (recurrence-free survival) were performed.
Results: We observed that the presence of increased stromal CD163+ macrophages is associated with poorer recurrence-free survival in luminal type A cancers (hazard ratio=1.47, p=0.044). In contrast, increased stromal CD163+ macrophages is associated with improved recurrence-free survival in luminal type B cancers (hazard ratio=0.702, p=0.047) and basal type cancers (hazard ratio=0.656, p=0.13). Kaplan-Meier survival analyses, with the cases stratified into quartiles based on relative macrophage densities in each molecular subtype, are shown in Figure 1.
Figure 1: Kaplan-Meier survival analysis (recurrence-free survival) of stromal macrophage density in different molecular subtypes.
Conclusions: Our study demonstrated differing prognostic associations for increased stromal macrophages in the different molecular subtypes of breast cancers. We have currently extended the same analysis to a large validation series of 1722 breast cancers (subtyped by gene expression profiling and immunohistochemistry) and the results will be updated.
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 24, Monday Morning