DISTINCT ANGIOGENIC PATTERNS ARE ASSOCIATED WITH HIGH-GRADE IN-SITU DUCTAL CARCINOMAS OF THE BREAST

Angiogenesis, the formation of new blood vessels from the existing vas cular network, has been demonstrated to be an important prognostic fac tor in invasive breast carcinoma. The switch to an angiogenic phenotyp e represents a growth-limiting step during carcinogenesis and might, i n pre-invasive lesions, indicate the risk for developing an invasive p henotype. The discrepancy between modern therapy options for invasive breast carcinomas and the relatively aggressive treatment of in situ l esions underlines the need for such prognostic factors for ductal in s itu breast carcinomas (DCIS). Patterns of vascularity were examined in 75 formalin-fixed, paraffin-embedded DCIS by immunohistochemical stai ning 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 combinat ion of both. Two distinct vascular patterns, were observed: a diffuse increase of stromal vascularity between duct lesions (pattern I), whic h was present alone in 8/75 (11 per cent), and a dense rim of microves sels 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 I and 62 per cent (47/75) showed pattern II. There was a significant correlation between these pattersn (P=0.0001; chi(2)=15 .1), such that both mere 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 t he rim of vessels and another generated indirectly via recruitment of accessory cells such as macrophage and endothelial cells, which themse lves release other angiogenic factors, causing the increase of stromal vascularity. A significant increase in both stromal vascularity (patt ern I) and the presence of a rim (pattern II) was observed in high-gra de DCIS lesions (P=0.005 and P=0.037). Indeed, all the patient relapse s occurred in these high-grade lesions, but due to the small number of patient events, no significant correlation of vascular pattern to sur vival was observed (P>0.05). This study suggests that distinct pattern s of vascularity in DCIS might be useful for identifying patients who are at risk of relapse.