title: Myofibroblastic stromal reaction and lymph node status in invasive breast carcinoma: possible role of the TGF-β1/TGF-βR1 pathway.
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.
authors.affiliation: Department of Pathology, Institute of Pathology and Genetics, 25, Avenue Georges Lemaître, Gosselies 6041, Belgium. xavier.catteau06@gmail.com.
authors.forename: Xavier
authors.initials: X
authors.lastname: Catteau
authors.forename: Philippe
authors.initials: P
authors.lastname: Simon
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Noël
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism* / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism*; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D000199:Actins; D018952:Antigens, CD34; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I