Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer

Lebok,Patrick; Huber,Julia; Burandt,Eike‑Christian; Lebeau,Annette; Marx,Andreas Holger; Terracciano,Luigi; Heilenkötter,Uwe; Jänicke,Fritz; Müller,Volkmar; Paluchowski,Peter; Geist,Stefan; Wilke,Christian; Simon,Ronald; Sauter,Guido; Quaas,Alexander

doi:10.3892/mmr.2016.5430

Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer

Authors:
- Patrick Lebok
- Julia Huber
- Eike‑Christian Burandt
- Annette Lebeau
- Andreas Holger Marx
- Luigi Terracciano
- Uwe Heilenkötter
- Fritz Jänicke
- Volkmar Müller
- Peter Paluchowski
- Stefan Geist
- Christian Wilke
- Ronald Simon
- Guido Sauter
- Alexander Quaas
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Affiliations: Institute of Pathology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Institute of Pathology, University Hospital Basel, 4056 Basel, Switzerland, Department of Gynaecology, Hospital Itzehoe, D-25524 Itzehoe, Germany, Department of Gynaecology, Hospital Pinneberg, D-25421 Pinneberg, Germany, Department of Gynaecology, University Medical Centre Hamburg‑Eppendorf, D‑20246 Hamburg, Germany, Department of Gynaecology, Hospital Elmshorn, D-25337 Elmshorn, Germany, Institute for Pathology, University of Cologne, D‑50937 Cologne, Germany
Published online on: June 23, 2016 https://doi.org/10.3892/mmr.2016.5430
Pages: 1443-1450
Copyright: © Lebok et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Angiogenesis is a key process in tumor growth and progression, which is controlled by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). In order to better understand the prevalence and prognostic value of VEGFR1 expression in breast cancer, a tissue microarray containing >2,100 breast cancer specimens, with clinical follow‑up data, was analyzed by immunohistochemistry using an antibody directed against the membrane‑bound full‑length receptor protein. The results demonstrated that membranous VEGFR1 staining was detected in all (5 of 5) normal breast specimens. In carcinoma specimens, membranous staining was negative in 3.1%, weak in 6.3%, moderate in 10.9%, and strong in 79.7% of the 1,630 interpretable tissues. Strong staining was significantly associated with estrogen receptor and progesterone receptor expression, but was inversely associated with advanced tumor stage (P=0.0431), high Bloom-Richardson-Ellis Score for Breast Cancer grade and low Ki67 labeling index (both P<0.0001). Cancers with moderate to strong (high) VEGFR1 expression were associated with significantly improved overall survival, as compared with tumors exhibiting negative or weak (low) expression (P=0.0015). This association was also detected in the subset of nodal‑positive cancers (P=0.0018), and in the subset of 185 patients who had received tamoxifen as the sole therapy (P=0.001). In conclusion, these data indicated that membrane‑bound VEGFR1 is frequently expressed in normal and cancerous breast epithelium. In addition, reduced or lost VEGFR1 expression may serve as a marker for poor prognosis in patients with breast cancer, who might not optimally benefit from endocrine therapy.

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