Nestin-positive microvessel density is an independent prognostic factor in breast cancer

Nowak,Aleksandra; Grzegrzolka,Jedrzej; Paprocka,Maria; Piotrowska,Aleksandra; Rys,Janusz; Matkowski,Rafal; Dziegiel,Piotr

doi:10.3892/ijo.2017.4057

Nestin-positive microvessel density is an independent prognostic factor in breast cancer

Authors:
- Aleksandra Nowak
- Jedrzej Grzegrzolka
- Maria Paprocka
- Aleksandra Piotrowska
- Janusz Rys
- Rafal Matkowski
- Piotr Dziegiel
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Affiliations: 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, Department of Tumour Pathology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Cracow Branch, Wroclaw, Poland, Breast Unit, Department of Surgical Oncology, Lower Silesian Oncology Centre, Wroclaw, Poland
Published online on: June 26, 2017 https://doi.org/10.3892/ijo.2017.4057
Pages: 668-676

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Abstract

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.

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