The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions

被引:48
作者
Pavlakis, Kitty [1 ]
Messini, Irene [2 ]
Vrekoussis, Thomas [3 ]
Yiannou, Petros [2 ]
Keramopoullos, Dimitrios [4 ]
Louvrou, Niki [4 ]
Liakakos, Theodoros [5 ]
Stathopoulos, Efstathios N. [3 ]
机构
[1] Univ Athens, Sch Med, Dept Pathol, GR-11527 Athens, Greece
[2] IASO Hosp, Dept Pathol, Athens, Greece
[3] Univ Crete, Dept Pathol, Sch Med, Iraklion, Crete, Greece
[4] IASO Hosp, Breast Surg Clin, Athens, Greece
[5] Univ Hosp ATTIKON, Surg Clin 3, Athens, Greece
关键词
D O I
10.1186/1471-2407-8-88
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Conclusion: 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.
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