title: The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions.
abstract: BACKGROUND
  To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions.
  
  
  METHODS
  78 in situ ductal carcinomas of all degrees of differentiation, 22 atypical ductal hyperplasias, 25 in situ lobular carcinomas, 18 atypical lobular hyperplasias, 32 ductal epithelial hyperplasias of usual type and 8 flat atypias were immunohistochemically investigated for the expression of vascular endothelial growth factor (VEGF), smooth muscle actin (SMA) and CD34, while microvessel density (MVD) was counted using the anti-CD31 antibody.
  
  
  RESULTS
  VEGF expression was strongly correlated with MVD in all hyperplastic and pre-invasive breast lesions (p < 0.05). Stromagenesis, as characterized by an increase in SMA and a decrease in CD34 positive myofibroblasts was observed mostly around ducts harboring high grade in situ carcinoma and to a lesser extent around moderately differentiated DCIS. In these two groups of in situ carcinomas, a positive correlation between MVD and SMA (p < 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p < 0.05). No statistically significant changes of the stromal fibroblasts were observed in low grade DCIS neither in any of the other lesions under investigation as compared to normal mammary intra- and interlobular stroma.
  
  
  CONCLUSIONS
  Angiogenesis is observed before any significant fibroblastic stromagenesis in pre-invasive breast lesions. A composite phenotype characterized by VEGF positive epithelial cells and SMA positive/CD34 negative stromal cells, is identified mostly in intermediate and high grade DCIS. These findings might imply for new therapeutic strategies using both anti-angiogenic factors and factors selectively targeting tumor stroma in order to prevent the progression of DCIS to invasive carcinoma.
authors.affiliation: Pathology Department, Medical School, University of Athens, Athens, Greece. epavlaki@med.uoa.gr
authors.forename: Kitty
authors.initials: K
authors.lastname: Pavlakis
authors.forename: Irene
authors.initials: I
authors.lastname: Messini
authors.forename: Thomas
authors.initials: T
authors.lastname: Vrekoussis
authors.forename: Petros
authors.initials: P
authors.lastname: Yiannou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Keramopoullos
authors.forename: Niki
authors.initials: N
authors.lastname: Louvrou
authors.forename: Theodoros
authors.initials: T
authors.lastname: Liakakos
authors.forename: Efstathios N
authors.initials: EN
authors.lastname: Stathopoulos
mesh_terms: D000199:Actins / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D001940:Breast / Q000473:pathology; D001941:Breast Diseases / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000378:metabolism*; D018275:Carcinoma, Lobular / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D009130:Muscle, Smooth; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D000199:Actins; D018952:Antigens, CD34; D042461:Vascular Endothelial Growth Factor A