Vascular proliferation is increased in basal-like breast cancer

Abstract

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.

Evaluation of Vascular Proliferation in Molecular Subtypes of Breast Cancer

“…Our results are in line with previous reports that found increased vascular proliferation in basal-like breast tumors, but using different markers of vascular proliferation (18)(19)(20). The mechanism of this association is not known, although some authors suggest that vascular endothelial growth factor (VEGF), as a regulator of angiogenesis, contributes to increased vascular proliferation in basal-like tumors (18,22). Basal-like tumors are associated with a high rate of hematogenous metastasis and with the poorest prognosis among all molecular groups.…”

“…Previous studies showed that vascular proliferation is a sensitive method for evaluation of angiogenesis, with more reliable results compared with standard MVD (18)(19)(20)(21). MVP is a relatively new parameter of angiogenesis that measures the most active tumor vasculature, while MVD includes both preformed and newly formed vessels (6,7).…”

“…MVP is a relatively new parameter of angiogenesis that measures the most active tumor vasculature, while MVD includes both preformed and newly formed vessels (6,7). Thus, vascular proliferation reflects ongoing angiogenesis by reducing the possibility of counting vessels that are not produced by the tumor (18).…”

Decreased Vascular Endothelial Growth Factor Expression Is Associated With Cell Apoptosis in Low-Dose Aspirin-Induced Gastric Mucosal Injury

“…For each section, the degree of IHC staining was assessed using a semiquantitative and subjective scoring system that took into consideration the proportion of cells expressing VEGF as well as the intensity of staining. 20,21 The percentage of VEGF-positive cells was scored on a scale of 0 (,4%), 1 (5%-24%), 2 (25%-49%), 3 (50%-74%) and 4 (75%-100%). Staining intensity was graded on a scale of 0 (negative), 1 (weak), 2 (moderate) and 3 (strong).…”

Molecular Hierarchy of Heparin-Binding EGF-like Growth Factor–Regulated Angiogenesis in Triple-Negative Breast Cancer

“…Recently, numerous studies have indicated that angiogenesis plays an important role in the pathogenesis of TNBC (8)(9)(10), leading to the development of a number of novel, targeted therapies. In 2008, the U.S. Food and Drug Administration approved the use of bevacizumab (Avastin; Genentech), a humanized monoclonal antibody, plus paclitaxel, as first-line therapy in patients with metastatic breast cancer.…”