Core needle biopsy changes the expression of TGFβ1 and TGFβRII at protein level, and the distribution of CD4 and CD8 positive T cells in primary breast cancer

Pathol Res Pract. 2024 Aug:260:155428. doi: 10.1016/j.prp.2024.155428. Epub 2024 Jul 1.

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.

Keywords: Breast cancer; CD4; CD8; Core needle biopsy; TGFβ1; TGFβRII.

MeSH terms

  • Adult
  • Aged
  • Biopsy, Large-Core Needle
  • Breast Neoplasms* / immunology
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • CD4-Positive T-Lymphocytes* / metabolism
  • CD8-Positive T-Lymphocytes* / immunology
  • CD8-Positive T-Lymphocytes* / metabolism
  • CD8-Positive T-Lymphocytes* / pathology
  • Female
  • Humans
  • Middle Aged
  • Receptor, Transforming Growth Factor-beta Type II* / metabolism
  • Transforming Growth Factor beta1* / metabolism
  • Tumor Microenvironment* / immunology

Substances

  • Receptor, Transforming Growth Factor-beta Type II
  • Transforming Growth Factor beta1
  • TGFB1 protein, human
  • TGFBR2 protein, human