Myofibroblastic stromal reaction and lymph node status in invasive breast carcinoma: possible role of the TGF-β1/TGF-βR1 pathway

Background: The microenvironment modulates tissue specificity in the normal breast and in breast cancer. The stromal loss of CD34 expression and acquisition of SMA myofibroblastic features may constitute a prerequisite for tumor invasiveness in breast carcinoma. The aim of the present study is to examine the stromal expression of CD34 and SMA in cases of invasive ductal carcinoma and to try to demonstrate the role played by the TGF-beta 1 et TGF-beta R1 pathway in the transformation of normal breast fibrocytes into myofibroblasts. Methods: We carried out an immunohistochemical study of CD34, SMA, TGF-beta and TGF-beta R1 on a series of 155 patients with invasive ductal carcinoma. We also treated a breast fibrocytes cell line with TGF-beta 1. Results: We found a loss of stromal expression of CD34 with the appearance of a myofibroblastic reaction in almost 100% cases of invasive ductal carcinoma. The strong stromal expression of SMA correlates with the presence of lymph node metastases. We were also able to show a greater expression of TGF-beta in the tumor cells as well as a higher expression of TGF-beta R1 in the tumor stroma compared to normal breast tissue. Finally, we demonstrated the transformation of breast fibrocytes into SMA positive myofibroblasts after being treated with TGF-beta 1. Conclusions: Our study demonstrated that a significant tumor myofibroblastic reaction is correlated with the presence of lymph node metastasis and that this myofibroblastic reaction can be induced by TGF-beta 1. Future research on fibrocytes, myofibroblasts, TGF-beta and stromal changes mechanisms is essential in the future and may potentially lead to new treatment approaches.