Valković Toni, Dobrila Frane, Melato Mauro, Sasso Franco, Rizzardi Clara, Jonjić Nives
Department of Pathology, Medical Faculty, University of Rijeka, B. Branchetta 20, 51000 Rijeka, Croatia.
Virchows Arch. 2002 Jun;440(6):583-8. doi: 10.1007/s004280100458. Epub 2001 May 16.
Angiogenic and anti-angiogenic factors, secreted by tumor, inflammatory, and stromal cells play an important role in regulation of neovascularization. Among the most important of these is vascular endothelial growth factor (VEGF), a specific mitogen for endothelium, which increases vascular permeability and induces proteolytic enzymes necessary for vascular remodeling. Tumor-associated macrophages (TAMs) can express complex functions related to tumor biology, including growth, proliferative rate, stroma formation and dissolution, and neovascularization. The aim of this study was to define, using immunohistochemical analysis, the microvessel density (MVD), VEGF expression, and TAMs level in 97 human invasive ductal breast carcinomas not otherwise specified (NOS), investigate a possible relationship between them and then correlate their values with tumor grade, mitotic activity index (MAI), tumor size and lymph-node status. Statistical analysis showed a strong positive relationship between MVD and VEGF expression ( P<0.001). Furthermore, both MVD and VEGF expression were significantly correlated with tumor grade and lymph-node status, and TAMs infiltration with MAI. TAM level showed a significant positive connection with VEGF expression and MVD. These in situ observations suggest that VEGF stimulates angiogenesis in human invasive ductal breast carcinoma NOS and attracts macrophages to the tumor locus, which then may be involved in angiogenesis promotion. The expression of this angiogenic molecule, and MVD and TAM level, can provide additional prognostic significance and help in the identification of patients who need postoperative adjuvant therapy.
肿瘤、炎症和基质细胞分泌的血管生成因子和抗血管生成因子在新血管形成的调节中发挥着重要作用。其中最重要的是血管内皮生长因子（VEGF），它是一种内皮细胞特异性有丝分裂原，可增加血管通透性并诱导血管重塑所需的蛋白水解酶。肿瘤相关巨噬细胞（TAM）可表达与肿瘤生物学相关的复杂功能，包括生长、增殖率、基质形成与溶解以及新血管形成。本研究的目的是通过免疫组织化学分析确定97例未另作说明（NOS）的人浸润性导管乳腺癌中的微血管密度（MVD）、VEGF表达和TAM水平，研究它们之间可能存在的关系，然后将其值与肿瘤分级、有丝分裂活性指数（MAI）、肿瘤大小和淋巴结状态相关联。统计分析显示MVD与VEGF表达之间存在强正相关（P<0.001）。此外，MVD和VEGF表达均与肿瘤分级和淋巴结状态显著相关，TAM浸润与MAI显著相关。TAM水平与VEGF表达和MVD呈显著正相关。这些原位观察结果表明，VEGF刺激人浸润性导管乳腺癌NOS中的血管生成，并将巨噬细胞吸引至肿瘤部位，巨噬细胞随后可能参与促进血管生成。这种血管生成分子的表达、MVD和TAM水平可为预后提供额外的意义，并有助于识别需要术后辅助治疗的患者。
