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Open Access Research article

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

Xavier Catteau12*, Philippe Simon23 and Jean-Christophe Noël24

Author Affiliations

1 Department of Pathology, Institute of Pathology and Genetics, 25, Avenue Georges Lemaître, Gosselies 6041, Belgium

2 Faculty of Medicine, Université Libre de Bruxelles, Brussels, Belgium

3 Gynecology Unit, Erasme University Hospital-Université Libre de Bruxelles, Brussels, Belgium

4 Gynecopathology Unit, Pathology Department, Erasme University Hospital-Université Libre de Bruxelles, Brussels, Belgium

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BMC Cancer 2014, 14:499  doi:10.1186/1471-2407-14-499

Published: 9 July 2014

Abstract

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-ß 1 et TGF-ß R1 pathway in the transformation of normal breast fibrocytes into myofibroblasts.

Methods

We 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.

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-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.

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-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.

Keywords:
Breast carcinoma; Tumor microenvironment; Fibrocytes; Myofibroblasts; SMA; CD34; TGF-ß; Metastasis; Lymph node