Abstract
BackgroundThe 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-ß 1 et TGF-ß R1 pathway in the transformation of normal breast fibrocytes into myofibroblasts.MethodsWe carried out an immunohistochemical study of CD34, SMA, TGF-ß and TGF-ß R1 on a series of 155 patients with invasive ductal carcinoma. We also treated a breast fibrocytes cell line with TGF-ß1.ResultsWe 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-ß in the tumor cells as well as a higher expression of TGF- ß 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-ß1.ConclusionsOur 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-ß1. Future research on fibrocytes, myofibroblasts, TGF-ß and stromal changes mechanisms is essential in the future and may potentially lead to new treatment approaches.
Highlights
The microenvironment modulates tissue specificity in the normal breast and in breast cancer
The present study aims to investigate this phenomenon in cases of invasive ductal carcinoma (IDC) and to try to understand the underlying mechanism responsible for this myofibroblastic reaction, especially the role played by Transforming growth-beta (TGF-ß)
This phenomenon is almost constant and more than likely plays an important tumoral role, in the invasion process. Importantly, this pro-invasive action seems to be confirmed by the fact that an intense expression of smooth muscle actin (SMA) myofibroblasts was correlated with the presence of lymph node metastasis
Summary
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-ß 1 et TGF-ß R1 pathway in the transformation of normal breast fibrocytes into myofibroblasts. The microenvironment modulates normal breast tissue, as well as the growth, survival, polarity, and invasive behavior of breast cancer cells [2,3]. The stromal loss of CD34 expression and acquisition of smooth muscle actin (SMA) myofibroblastic features may constitute a prerequisite for tumor invasiveness in breast carcinoma [4,5]. The present study aims to investigate this phenomenon in cases of invasive ductal carcinoma (IDC) and to try to understand the underlying mechanism responsible for this myofibroblastic reaction, especially the role played by TGF-ß
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