title: Distinct angiogenic patterns are associated with high-grade in situ ductal carcinomas of the breast.
abstract: Angiogenesis, the formation of new blood vessels from the existing vascular network, has been demonstrated to be an important prognostic factor in invasive breast carcinoma. The switch to an angiogenic phenotype represents a growth-limiting step during carcinogenesis and might, in pre-invasive lesions, indicate the risk for developing an invasive phenotype. The discrepancy between modern therapy options for invasive breast carcinomas and the relatively aggressive treatment of in situ lesions underlines the need for such prognostic factors for ductal in situ breast carcinomas (DCIS). Patterns of vascularity were examined in 75 formalin-fixed, paraffin-embedded DCIS by immunohistochemical staining of vessels using antibodies against Factor VIII-related antigen. Histological classification was performed according to four different systems, based on architectural or cytonuclear features, or a combination of both. Two distinct vascular patterns were observed: a diffuse increase of stromal vascularity between duct lesions (pattern I), which was present alone in 8/75 (11 per cent), and a dense rim of microvessels adjacent to the basement membrane of individual ducts (pattern II), present alone in 12/75 (16 per cent). In total, 57 per cent (43/75) showed pattern 1 and 62 per cent (47/75) showed pattern II. There was a significant correlation between these patterns (P = 0.0001; chi 2 = 15.1), such that both were present in 35 (47 per cent). These different vascular patterns imply two angiogenic pathways: one pathway mediated by angiogenic factors released directly by tumour cells resulting in the rim of vessels and another generated indirectly via recruitment of accessory cells such as macrophage and endothelial cells, which themselves release other angiogenic factors, causing the increase of stromal vascularity. A significant increase in both stromal vascularity (pattern I) and the presence of a rim (pattern II) was observed in high-grade DCIS lesions (P = 0.005 and P = 0.037). Indeed, all the patient relapses occurred in these high-grade lesions, but due to the small number of patient events, no significant correlation of vascular pattern to survival was observed (P > 0.05). This study suggests that distinct patterns of vascularity in DCIS might be useful for identifying patients who are at risk of relapse.
authors.affiliation: Department of Cellular Science, John Radcliffe Hospital, University of Oxford, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Engels
authors.forename: S B
authors.initials: SB
authors.lastname: Fox
authors.forename: R M
authors.initials: RM
authors.lastname: Whitehouse
authors.forename: K C
authors.initials: KC
authors.lastname: Gatter
authors.forename: A L
authors.initials: AL
authors.lastname: Harris
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000098:blood supply* / Q000628:therapy; D002278:Carcinoma in Situ / Q000098:blood supply* / Q000556:secondary / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000098:blood supply* / Q000556:secondary / Q000628:therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011379:Prognosis