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乳腺放射状瘢痕和乳腺癌在参与血管基质形成的因子表达方面具有相似的改变。

Radial scars of the breast and breast carcinomas have similar alterations in expression of factors involved in vascular stroma formation.

作者信息

Jacobs Timothy W, Schnitt Stuart J, Tan Xiaolian, Brown Lawrence F

机构信息

Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.

出版信息

Hum Pathol. 2002 Jan;33(1):29-38. doi: 10.1053/hupa.2002.30190.

Abstract

We recently reported that radial scars are an independent histologic risk factor for breast cancer. The reason for this association is not known. Given the importance of stromal-epithelial interactions in the pathogenesis of breast cancer, we studied radial scars for the expression of a number of factors known to be involved in the formation of vascular stroma in breast cancer. In situ hybridization was performed on formalin-fixed paraffin sections using (35)S-labeled riboprobes for collagen type 1, total fibronectin, extra domain A (ED-A)+ fibronectin, thrombospondin 1, vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF), and one of its endothelial receptors, kinase insert domain-containing receptor (KDR) (vascular endothelial growth factor receptor [VEGFR-2]). Expression levels in radial scars (9 cases) were compared with those in normal breast tissue (15 cases) and infiltrating ductal breast carcinoma (4 cases). Factor VIII-related antigen immunostaining was used to define the distribution of microvessels in radial scars, carcinoma, and normal breast tissue. Compared with normal breast tissue, the radial scars showed focally increased numbers of blood vessels and focally increased expression of messenger RNA (mRNA) for collagen type 1, total fibronectin, ED-A+ fibronectin, thrombospondin 1, VPF/VEGF, and KDR. This pattern of mRNA overexpression was similar to that seen in the 4 invasive cancers. We conclude that there are similarities between radial scars and invasive breast cancers with regard to the level of mRNA expression for several factors involved in the formation of vascular stroma. These results suggest that a similar disturbance in stromal-epithelial interactions is present in both lesions.

摘要

我们最近报道,放射状瘢痕是乳腺癌的一个独立组织学危险因素。这种关联的原因尚不清楚。鉴于基质-上皮相互作用在乳腺癌发病机制中的重要性,我们研究了放射状瘢痕中一些已知参与乳腺癌血管基质形成的因子的表达情况。使用针对Ⅰ型胶原、总纤连蛋白、额外结构域A(ED-A)+纤连蛋白、血小板反应蛋白1、血管通透因子(VPF)/血管内皮生长因子(VEGF)及其内皮受体之一含激酶插入结构域受体(KDR)(血管内皮生长因子受体[VEGFR-2])的(35)S标记核糖探针,对福尔马林固定石蜡切片进行原位杂交。将放射状瘢痕(9例)中的表达水平与正常乳腺组织(15例)和浸润性导管癌(4例)中的表达水平进行比较。采用因子Ⅷ相关抗原免疫染色来确定放射状瘢痕、癌组织和正常乳腺组织中微血管的分布。与正常乳腺组织相比,放射状瘢痕显示血管数量局部增加,且Ⅰ型胶原、总纤连蛋白、ED-A+纤连蛋白、血小板反应蛋白1、VPF/VEGF和KDR的信使核糖核酸(mRNA)表达局部增加。这种mRNA过表达模式与4例浸润性癌中的情况相似。我们得出结论,在参与血管基质形成的几个因子的mRNA表达水平方面,放射状瘢痕与浸润性乳腺癌之间存在相似性。这些结果表明,这两种病变中存在相似的基质-上皮相互作用紊乱。

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