Abstract
Chronic inflammation is known to facilitate cancer progression and metastasis. Less is known about the effect of acute inflammation within the tumor microenvironment, resulting from standard invasive procedures. Recent studies in mouse models have shown that the acute inflammatory response triggered by a biopsy in mammary cancer increases the frequency of distal metastases. Although tumor biopsies are part of the standard clinical practice in breast cancer diagnosis, no studies have reported their effect on inflammatory response. The objective of this study is to (1) determine whether core needle biopsies in breast cancer patients trigger an inflammatory response, (2) characterize the type of inflammatory response present, and (3) evaluate the potential effect of any acute inflammatory response on residual tumor cells. The biopsy wound site was identified in the primary tumor resection tissue samples from breast cancer patients. The inflammatory response in areas adjacent (i.e., immediately around previous biopsy site) and distant to the wound biopsy was investigated by histology and immunohistochemistry analysis. Proliferation of tumor cells was also assayed. We demonstrate that diagnostic core needle biopsies trigger a selective recruitment of inflammatory cells at the site of the biopsy, and they persist for extended periods of time. While macrophages were part of the inflammatory response, an unexpected accumulation of eosinophils at the edge of the biopsy wound was also identified. Importantly, we show that biopsy causes an increase in the proliferation rate of tumor cells located in the area adjacent to the biopsy wound. Diagnostic core needle biopsies in breast cancer patients do induce a unique acute inflammatory response within the tumor microenvironment and have an effect on the surrounding tumor cells. Therefore, biopsy-induced inflammation could have an impact on residual tumor cell progression and/or metastasis in human breast cancer. These findings may carry relevance in the clinical management of breast cancer.
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Abbreviations
- H&E:
-
Hematoxylin and eosin
- IHC:
-
Immunohistochemistry
- CD (from CD45 or CD68):
-
Cluster of differentiation (cluster of differentiation 45 and cluster of differentiation 68)
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Acknowledgments
We wish to thank the staff of the Pathology Facility at the University of Vermont Medical Center for their assistance in retrieving archives tissue samples and providing the unstaining tissue slide section. We also thank Phani Gummadidala for technical support. This work was funded by the Virginia Wellington Cabot Foundation (M.R), Lake Champlain Cancer Research Organization (LLCRO) (T.J.) and NIH P30 RR031158 (M.R.).
Authors’ contribution
GS and AO contributed to the performance of experiments (e.g., immunostaining, identification of the biopsy area, manual quantification of number of cells in each area, etc.), the design of the study, acquisition of data, analysis and interpretation of the results, and involved in the drafting of the manuscript. BS and JW contributed to the performance of experiments (e.g., immunostaining, identification of the biopsy area, manual quantification of number of cells in each area, etc.), the design of the study, acquisition of data, analysis, and interpretation of the results. JB performed all final statistical analysis in the manuscript, and as involved in the drafting of the manuscript. AA (pathologist), he identified the eligible patients, verified the identification of the biopsy wound or identified the wound, verified the results from the immunostaining, participated in the interpretation of the data, and involved in the drafting of the manuscript. TJ contributed to the design of the study, evaluated the results, and involved in the drafting of the manuscript. MR contributed the design of the study, wrote the IRB protocol, participated in the identification of the biopsy area, evaluated the immunostaining results, participated in the analysis and interpretation of the results, and did most of the writing of the manuscript.
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Gabriela Szalayova and Aleksandra Ogrodnik are co-first authors and contributed equally to this work.
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Szalayova, G., Ogrodnik, A., Spencer, B. et al. Human breast cancer biopsies induce eosinophil recruitment and enhance adjacent cancer cell proliferation. Breast Cancer Res Treat 157, 461–474 (2016). https://doi.org/10.1007/s10549-016-3839-3
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DOI: https://doi.org/10.1007/s10549-016-3839-3