title: Radial scars of the breast and breast carcinomas have similar alterations in expression of factors involved in vascular stroma formation.
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.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Jacobs
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Xiaolian
authors.initials: X
authors.lastname: Tan
authors.forename: Lawrence F
authors.initials: LF
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D001940:Breast / Q000033:anatomy & histology / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000098:blood supply / Q000378:metabolism* / Q000556:secondary; D002921:Cicatrix / Q000378:metabolism* / Q000473:pathology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D053331:Ectodysplasins; D016228:Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008222:Lymphokines / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008833:Microcirculation / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D012313:RNA / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D024042:Collagen Type I; C506018:EDA protein, human; D053331:Ectodysplasins; D016228:Endothelial Growth Factors; D005353:Fibronectins; D008222:Lymphokines; D008565:Membrane Proteins; D012334:RNA, Neoplasm; D017978:Receptors, Growth Factor; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D012313:RNA; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor