Szalayova Gabriela, Ogrodnik Aleksandra, Spencer Brianna, Wade Jacqueline, Bunn Janice, Ambaye Abiy, James Ted, Rincon Mercedes
Department of Surgery, University of Vermont, Burlington, VT, 05405, USA.
Department of Surgery, Danbury Hospital, Danbury, CT, 06810, USA.
Breast Cancer Res Treat. 2016 Jun;157(3):461-74. doi: 10.1007/s10549-016-3839-3. Epub 2016 Jun 1.
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.
已知慢性炎症会促进癌症进展和转移。对于标准侵入性操作在肿瘤微环境中引发的急性炎症的影响,人们了解较少。最近在小鼠模型中的研究表明,乳腺癌活检引发的急性炎症反应会增加远端转移的频率。尽管肿瘤活检是乳腺癌诊断标准临床实践的一部分,但尚无研究报道其对炎症反应的影响。本研究的目的是:(1)确定乳腺癌患者的粗针活检是否会引发炎症反应;(2)描述所呈现的炎症反应类型;(3)评估任何急性炎症反应对残留肿瘤细胞的潜在影响。在乳腺癌患者的原发肿瘤切除组织样本中确定活检伤口部位。通过组织学和免疫组织化学分析研究伤口活检部位相邻(即紧邻先前活检部位周围)和远处区域的炎症反应。还检测了肿瘤细胞的增殖情况。我们证明,诊断性粗针活检会在活检部位引发炎症细胞的选择性募集,并且这些炎症细胞会持续较长时间。虽然巨噬细胞是炎症反应的一部分,但在活检伤口边缘还发现了嗜酸性粒细胞的意外聚集。重要的是,我们表明活检会导致活检伤口相邻区域的肿瘤细胞增殖率增加。乳腺癌患者的诊断性粗针活检确实会在肿瘤微环境中引发独特的急性炎症反应,并对周围肿瘤细胞产生影响。因此,活检诱导的炎症可能会影响人类乳腺癌中残留肿瘤细胞的进展和/或转移。这些发现可能与乳腺癌的临床管理相关。