The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions
The assessment of angiogenesis and fibroblastic stromagenesis in hyperplastic and pre-invasive breast lesions
复制标题
DOI：
10.1186/1471-2407-8-88
复制
发表时间：
2008-04-02
期刊：
影响因子：
3.8
通讯作者：
Stathopoulos, Efstathios N.
中科院分区：
文献类型：
--
作者：
Pavlakis, Kitty;Messini, Irene;Stathopoulos, Efstathios N.
背景资料：探讨乳腺增生性病变与浸润前病变不同形态学改变过程中肿瘤微环境的变化。各种分化程度的原位导管癌78例，非典型导管增生22例，原位小叶癌25例，非典型小叶增生18例，应用免疫组化方法检测了32例普通型导管上皮增生和8例扁平型导管上皮增生中血管内皮生长因子（VEGF）的表达，结果：VEGF在乳腺增生及浸润前病变中的表达与MVD密切相关（p < 0.05）。间质增生，其特征是SMA增加和CD 34阳性肌成纤维细胞减少，主要在含有高级别原位癌的导管周围观察到，在中等分化的DCIS周围观察到程度较低。两组原位癌中MVD与SMA呈正相关（p < 0.05）。CD 34与MVD呈负相关（p < 0.05）。间质成纤维细胞的统计学上没有显着的变化，观察到在低级别DCIS，也没有在任何其他病变的调查相比，正常乳腺内和小叶间stroma.Conclusion：血管生成前观察到任何显着的成纤维细胞stromagenesis在浸润前乳腺病变。以VEGF阳性上皮细胞和SMA阳性/CD 34阴性基质细胞为特征的复合表型主要见于中、高级别DCIS。这些发现可能意味着新的治疗策略，使用抗血管生成因子和选择性靶向肿瘤间质的因子，以防止DCIS进展为浸润性癌。
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.