Abstract:
Core needle biopsy (CNB) has become a paradigm in preoperative breast cancer (BC) diagnosis. Although considered safe, it is an invasive procedure, which changes the tumor microenvironment. It facilitates a tumor supportive immune response, induces epithelial-mesenchymal transition (EMT), and enables the release of circulating tumor cells. The cytokine Transforming Growth Factor β (TGFβ) with its pleiotropic immunologic functions has an important role in this process. The aim of this study was to clarify the specific impact of CNB on the activity of the TGFβ pathway in early BC. We compared formalin fixed paraffin embedded samples from CNBs to the corresponding surgical resection specimens (SRSs) of 49 patients with BC. We found that the expression of TGFβ1 at protein level was significantly higher in both tumor epithelial and benign stromal cells in the SRSs (p=0.001), whereas the expression of TGFβRII in tumor cells was lower (p=0.001). The frequency of intra tumoral CD8 and CD4 positive T lymphocytes was lower in SRSs (p=0081 and p=0001, respectively), while in the peripheral stroma their prevalence was increased (p=0001 and p=0012, respectively). Our results show that CNB changes the hallmarks of the TGFβ path way in early BC. These CNB-induced changes in the tumor and in its microenvironment suggest that the procedure may change the immunological anti-tumor response of the host.
摘要:
核心针活检(CNB)已成为术前乳腺癌(BC)诊断的范例。虽然被认为是安全的,这是一个侵入性的过程,改变了肿瘤的微环境.它促进肿瘤支持性免疫反应,诱导上皮-间质转化(EMT),并能够释放循环肿瘤细胞。具有多效免疫功能的细胞因子转化生长因子β(TGFβ)在此过程中具有重要作用。这项研究的目的是阐明CNB对早期BC中TGFβ途径活性的具体影响。我们将来自CNBs的福尔马林固定石蜡包埋样品与49例BC患者的相应手术切除标本(SRS)进行了比较。我们发现TGFβ1在蛋白质水平上的表达在SRSs中的肿瘤上皮和良性基质细胞中显著增高(p=0.001)。而TGFβRII在肿瘤细胞中的表达较低(p=0.001)。SRS中肿瘤内CD8和CD4阳性T淋巴细胞的频率较低(分别为p=0081和p=0001),而在外周基质中,其患病率增加(分别为p=0001和p=0012)。我们的结果表明,CNB改变了早期BC中TGFβ路径的标志。这些CNB诱导的肿瘤及其微环境的变化表明,该程序可能会改变宿主的免疫抗肿瘤反应。