Obesity Promotes Cooperation of Cancer Stem-Like Cells and Macrophages to Enhance Mammary Tumor Angiogenesis.

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.

Internal validation testing for new technologies: bringing telecytopathology into the mainstream.

Implementing new technology in the laboratory can improve processes and patient care, but compliance with regulatory requirements can be a significant hurdle to clear. This study provides a detailed procedure to address user training, competency assessment, and internal validation of telecytopathology simultaneously, while fulfilling regulatory requirements set forth by the College of American Pathologists and CLIA '88. Six pathologists participated in this study. Methods and materials used included a blind correlation study between diagnoses rendered via telecytopathology and via direct microscopy on 10 finalized fine needle aspiration (FNA) cases. The first step of this procedure involved each pathologist to render a diagnosis for each specimen using telecytopathology. The second step was to allow each pathologist to diagnose each specimen via direct microscopic review after a wait period of at least 6 weeks. The diagnoses rendered via telecytopathology were then compared to both the established final diagnoses and the secondary direct microscopic review diagnoses to examine interpathologist and intrapathologist reproducibility with a passing rate of 90% or better. Results of the study yielded an average concordance rate of 96.67% for interpathologist reproducibility and 95% for intrapathologist reproducibility across all participating pathologists. All participants passed the assessment with a rate of 90% or better, proving evidence of competency. This study confirmed user competency and validated telecytopathology as an effective tool for examining and diagnosing cytology FNA specimens remotely. It also satisfied regulatory compliance requirements to ensure high quality of diagnostic testing and patient care.

Focus on technology: How important is resolution in telecytopathology?

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). METHODS: 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 = .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.