Obesity is correlated with worsened prognosis and treatment resistance in breast cancer. Macrophage-targeted therapies are currently in clinical trials, however, little is known about how obesity may impact treatment efficacy. Within breast adipose tissue, obesity leads to chronic, macrophage-driven inflammation, suggesting that obese breast cancer patients may benefit from these therapies. Using a high fat diet model of obesity, we orthotopically transplanted cancer cell lines into the mammary glands of obese and lean mice. We quantified changes in tumor invasiveness, angiogenesis and metastasis, and examined the efficacy of macrophage depletion to diminish tumor progression in obese and lean mice. Mammary tumors from obese mice grew significantly faster, were enriched for cancer stem-like cells (CSCs) and were more locally invasive and metastatic. Tumor cells isolated from obese mice demonstrated enhanced expression of stem cell-related pathways including Sox2 and Notch2. Despite more rapid growth, mammary tumors from obese mice had reduced necrosis, higher blood vessel density, and greater macrophage recruitment. Depletion of macrophages in obese tumor-bearing mice resulted in increased tumor necrosis, reduced endothelial cells, and enhanced recruitment of CD8+ T cells compared to IgG-treated controls. Macrophages may be an important clinical target to improve treatment options for obese breast cancer patients.

BACKGROUND:The authors conducted an analysis of 2 telepathology systems with different resolutions to determine how resolution affects the pathologists' ability to provide preliminary diagnoses for fine-needle aspirations (FNA). METH-ODS: FNA cases evaluated by telepathology between February 1, 2011 and January 18, 2012 were reviewed. Concordance indices between preliminary and final diagnoses were calculated for cases assessed with two proprietary systems (the Remote Meeting Technologies iMedHD system and the Olympus NetCam system) using 3 diagnostic classifications (negative, atypical, and suspicious/positive). A Wilcoxon rank-sum test was used to compare the number of passes necessary to determine adequacy. RESULTS: In total, 298 NetCam cases and 26 iMedHD cases were evaluated. The concordance index, which was calculated using the 3 classifications, was 0.943 (95% confidence interval, 0.922-0.963) for NetCam compared with 0.951 (95% confidence interval, 0.898-1.000) for iMedHD. The mean value for the number of passes required to determine adequacy was 2.2 for NetCam and 2.1 for iMedHD (P 5.838). CONCLUSIONS: The results from statistical analyses demonstrated no difference in the concordance indices between preliminary and final diagnoses or in the number of passes necessary to render adequacy between the 2 telepathology systems. However, because it had higher resolution along with other features, the iMedHD system achieved greater user satisfaction. Cancer (Cancer Cytopathol) 2014;122:546-52. V C 2014 American Cancer Society.KEY WORDS: telepathology; telecytopathology; immediate evaluations; preliminary diagnoses; fine-needle aspirations. INTRODUCTIONTelepathology is defined by the College of American Pathologists as the practice of pathology in which a pathologist views digitized or analog images (video or still) and renders an interpretation for inclusion in a formal diagnostic report or for documentation in the patient record. The College of American Pathologists further categorizes telepathology into different modes, including static telepathology (interpretation based on preselected, still images), dynamic telepathology (viewing real-time images), and whole-slide imaging.1 The use of telepathology as an educational and diagnostic tool has been on the rise since the mid 1980s. 2,3 It has recently proven to be sufficient for making timely and accurate preliminary diagnoses of specimens obtained by fine-needle aspiration (FNA). 2,4-6 For the purposes of this article, this technology is referred to hereinafter as telecytopathology, because it is solely used for the assessment FNA specimens. Studies increasingly are demonstrating high concordance and accuracy rates for preliminary diagnoses provided by dynamic telecytopathology versus direct microscopic evaluation. One 2008 study reported a Original Article diagnostic concordance rate of 97% and a diagnostic accuracy of 99% when comparing diagnoses rendered by telecytopathology with the original diagnoses of previously finalized cases. 4 Alsharif et al observ...

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Obesity is a growing health concern worldwide and increases the incidence of multiple types of cancer, including breast cancer. Obese breast cancer patients often develop more aggressive tumors than lean patients and have increased risk for metastasis, tumor recurrence and mortality. Here, we sought to address how obesity alters the biology of breast cancer to promote aggressive tumors. To induce obesity, we fed mice either a control diet (CD) or high fat diet (HFD) for 16 weeks, then transplanted Met-1 tumor cells into mammary fat pads and monitored tumor growth. At end stage, tumors from HFD-fed mice were significantly larger than tumors from CD-fed mice, suggesting obesity promotes tumor growth. To investigate how obesity promotes tumor aggression, we dissociated the tumors from CD- and HFD-fed mice and plated isolated tumor cells in tumorsphere and invasion assays to test for cells with cancer stem-like cell (CSC) properties. Tumor cells from HFD-fed mice demonstrated increased tumorsphere formation and increased capacity for invasion compared to tumor cells from CD-fed mice, suggesting that obesity selects for tumor cells with CSC properties. Next, to address how obesity impacts the tumor microenvironment, we evaluated tumor necrosis and blood vessel formation through CD31 staining. Tumors from HFD-fed mice had significantly less necrosis and greater CD31 staining than those from CD-fed mice, suggesting that obesity promotes tumor angiogenesis. Since obesity promotes chronic, macrophage-driven inflammation within adipose tissue of the mammary gland, we stained tumors for the macrophage marker, F4/80. As with obese mammary glands, tumors from HFD-fed mice had significantly greater macrophage recruitment than tumors from CD-fed mice, together suggesting that obesity alters the tumor microenvironment. To determine how obesity stimulates tumor angiogenesis, we performed an in vitro assay by culturing dissociated tumor cells from HFD or CD-fed mice alone or with macrophages. Conditioned media (CM) isolated from tumor cells from HFD-fed mice cultured with macrophages enhanced the ability of endothelial cells to form networks in vitro. In contrast, CM from HFD tumor cells alone, macrophages alone, or those from CD-fed mice did not promote network formation. Together, these results suggest that cooperation between macrophages and tumor cells from HFD-fed mice promotes angiogenesis. Next, to investigate how macrophages and tumor cells interacting in obesity, we depleted macrophages using anti-F4/80 antibodies in CD-fed and HFD-fed tumor-bearing mice. In HFD-fed mice, macrophage depletion significantly reduced tumor volume and CD31 staining while increasing tumor necrosis compared to controls. Obesity promotes interactions between tumor cells and macrophages to enhance tumor angiogenesis and progression.