Section for Pathology, The Gade Institute, University of Bergen, Haukeland University Hospital, 5021 Bergen, Norway.
Breast Cancer Res Treat. 2011 Dec;130(3):1063-71. doi: 10.1007/s10549-011-1740-7. Epub 2011 Aug 28.
Based on molecular sub-classification, basal-like breast cancer is associated with aggressive behavior. These tumors are frequently triple negative and lack traditional treatment targets. Angiogenesis, one of the hallmarks of cancer, is important for the local growth and spread of malignant tumors and is now a treatment target. The aim of this study was to explore whether angiogenesis is increased in relation to certain molecular subtypes of breast cancer with special focus on the basal-like category. Altogether, we analyzed a total of 431 breast cancers from two independent series after dual immunohistochemical staining of Factor VIII for endothelial cells and Ki-67 for proliferating cells. We then determined vascular proliferation in the most vascularized areas of the tumor. In both Series I and II, high vascular proliferation index (VPI) was significantly associated with expression of cytokeratin 5/6 (P = 0.001, 0.010), P-cadherin (P < 0.0005, <0.0005), epidermal growth factor receptor (P = 0.003, 0.001), the basal-like subtype (P = 0.001, 0.011), and the core basal phenotype (P = 0.002, 0.002), respectively. In Series I, high VPI was associated with the triple negative phenotype (P = 0.004) and p63 expression (P = 0.008). Tumor angiogenesis, as measured by vascular proliferation, was increased in the basal-like subtype in two independent breast cancer series and may thus be a possible treatment target in this category. Studies are required to evaluate whether this novel angiogenesis marker can be used to stratify patients for anti-angiogenesis treatment.
基于分子亚型分类,基底样乳腺癌与侵袭性行为相关。这些肿瘤通常是三阴性的,缺乏传统的治疗靶点。血管生成是癌症的标志之一,对于恶性肿瘤的局部生长和扩散非常重要,现已成为治疗靶点。本研究旨在探讨血管生成是否与乳腺癌的某些分子亚型相关,特别是基底样亚型。我们总共对来自两个独立系列的 431 例乳腺癌进行了双重免疫组化染色,分别检测内皮细胞的因子 VIII 和增殖细胞的 Ki-67。然后,我们确定了肿瘤最血管化区域的血管增殖情况。在两个系列中,高血管增殖指数(VPI)与细胞角蛋白 5/6(P=0.001,0.010)、P-钙黏蛋白(P<0.0005,<0.0005)、表皮生长因子受体(P=0.003,0.001)、基底样亚型(P=0.001,0.011)和核心基底表型(P=0.002,0.002)的表达显著相关。在系列 I 中,高 VPI 与三阴性表型(P=0.004)和 p63 表达(P=0.008)相关。在两个独立的乳腺癌系列中,基底样亚型的肿瘤血管生成(通过血管增殖来衡量)增加,因此可能成为该类别的一个潜在治疗靶点。需要进一步研究来评估这种新的血管生成标志物是否可用于分层患者进行抗血管生成治疗。