Department of Histology and Embryology, Wroclaw Medical University, Wroclaw, Poland.
Laboratory of Cellular Interactions, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
Int J Oncol. 2017 Aug;51(2):668-676. doi: 10.3892/ijo.2017.4057. Epub 2017 Jun 26.
The process of angiogenesis based on new vessel formation within the tumour area plays a significant role in the progression of breast cancer. Nestin is an intermediate filament protein and participates in the cytoskeleton organization. Nestin expression in the endothelium of blood vessels is mainly limited to newly forming vessels, thus being a more specific marker of angiogenesis than the commonly used vascular antigens. The aim of this study was to determine the prognostic value of nestin-positive microvessel density (Nes+MVD) in breast cancer patients and to confirm that nestin expression is related to newly forming tumour vessels. In this study, 137 cases of ductal breast carcinoma and 19 cases of non-malignant breast tissue lesions (NBTLs) were examined. Immunohistochemical reactions were performed on paraffin sections using antibodies against nestin, CD34 and CD31 antigens. For each marker, the microvessel density (MVD) was determined. Nestin expression was also examined in human endothelial cell lines (HUVEC-SVT, HMEC-1 and HEPC-CB.1) representing a different level of endothelial cell maturity. HUVEC-SVT and HMEC-1 cells represent the endothelium of mature vessels, whereas HEPC-CB.1 cells represent the early endothelial progenitor cells (EPCs). We have demonstrated that high Nes+MVD may be associated with a more aggressive course of the disease and a poorer prognosis. We have also found a higher Nes+MVD in the cases with lymph node metastases, with higher histological grade, with advanced-stage disease and with the triple-negative (TN) breast cancer. In addition, nestin expression in vessels was associated with a shorter overall survival (OS) and earlier relapse, and in the case of OS nestin was an independent prognostic factor. Finally, we further confirmed that nestin expression in endothelial cells reflects a progenitor nature of newly forming vessels.
肿瘤区域内新血管的形成是血管生成的过程，在乳腺癌的进展中起着重要作用。巢蛋白是一种中间丝蛋白，参与细胞骨架的组织。巢蛋白在内皮细胞中的表达主要局限于新形成的血管，因此比常用的血管抗原更能特异性地标记血管生成。本研究旨在确定巢蛋白阳性微血管密度（Nes+MVD）在乳腺癌患者中的预后价值，并证实巢蛋白表达与新形成的肿瘤血管有关。在这项研究中，检查了 137 例导管乳腺癌和 19 例非恶性乳腺组织病变（NBTLs）。使用针对巢蛋白、CD34 和 CD31 抗原的抗体对石蜡切片进行免疫组织化学反应。对于每个标志物，都确定了微血管密度（MVD）。还在代表不同内皮细胞成熟程度的人内皮细胞系（HUVEC-SVT、HMEC-1 和 HEPC-CB.1）中检查了巢蛋白的表达。HUVEC-SVT 和 HMEC-1 细胞代表成熟血管的内皮，而 HEPC-CB.1 细胞代表早期内皮祖细胞（EPCs）。我们已经证明，高 Nes+MVD 可能与疾病更具侵袭性和预后更差相关。我们还发现，淋巴结转移、组织学分级较高、疾病晚期和三阴性（TN）乳腺癌的病例中，Nes+MVD 较高。此外，血管中的巢蛋白表达与总生存期（OS）较短和更早复发有关，在 OS 中，巢蛋白是一个独立的预后因素。最后，我们进一步证实，内皮细胞中的巢蛋白表达反映了新形成血管的祖细胞性质。
