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

<p>Abstract</p> <p>Background</p> <p>To investigate the changes of the neoplastic microenvironment during the different morphological alterations of hyperplastic and pre-invasive breast lesions.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Clinical course and treatment results of breast cancer patients with ten or more positive axillary nodes

Two-hundred and fifty-nine women with operable breast cancer, having more than 10 involved nodes without a distant metastasis, were treated with radical, modified radical or partial mastectomy with complete axillary dissection. Survival at 5 years was 63% and at 7 years 54%. Fifty-six per cent and 52% were disease free 5 and 7 years after initial therapy. Postmenopausal women had an overall survival rate of 64% and disease free survival rate of 61% while premenopausal women had an overall survival of 58% and disease free survival of 52%. Survival and disease free survival rate for those with 10-20 positive nodes were 65% and 69% respectively, while for those with more than 20 positive nodes the rates were 49% and 52% respectively; a statistically better survival in the 2nd group. Although the observational time of patients having adjuvant CEF is short, a better survival rate and disease free survival rate is possible in women treated with CEF. (C) 2000 Harcourt Publishers Ltd

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

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 &lt; 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 &lt; 0.05) was observed. On the contrary, CD34 was found to be inversely related to MVD (p &lt; 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. © 2008 Pavlakis et al; licensee BioMed Central Ltd