title: In situ validation of VEGFR-2 and α v ß 3 integrin as targets for breast lesion characterization.
abstract: Vascular endothelial growth factor receptor 2 (VEGFR-2) and α v ß 3 integrin are the most frequently addressed targets in molecular imaging of tumor angiogenesis. In preclinical studies, molecular imaging of angiogenesis has shown potential to detect and differentiate benign and malignant lesions of the breast. Thus, in this retrospective clinical study employing patient tissues, the diagnostic value of VEGFR-2, α v ß 3 integrin and vascular area fraction for the diagnosis and differentiation of breast neoplasia was evaluated. To this end, tissue sections of breast cancer (n = 40), pre-invasive ductal carcinoma in situ (DCIS; n = 8), fibroadenoma (n = 40), radial scar (n = 6) and normal breast tissue (n = 40) were used to quantify (1) endothelial VEGFR-2, (2) endothelial α v ß 3 integrin and (3) total α v ß 3 integrin expression, as well as (4) the vascular area fraction. Sensitivity and specificity to differentiate benign from malignant lesions were calculated for each marker by receiver operating characteristics (ROC) analyses. Whereas vessel density, as commonly used, did not significantly differ between benign and malignant lesions (AUROC: 0.54), VEGFR-2 and α v ß 3 integrin levels were gradually up-regulated in carcinoma versus fibroadenoma versus healthy tissue. The highest diagnostic accuracy for differentiating carcinoma from fibroadenoma was found for total α v ß 3 integrin expression (AUROC: 0.76), followed by VEGFR-2 (AUROC: 0.71) and endothelial α v ß 3 integrin expression (AUROC: 0.68). In conclusion, total α v ß 3 integrin expression is the best discriminator between breast cancer, fibroadenoma and normal breast tissue. With respect to vascular targeting and molecular imaging of angiogenesis, endothelial VEGFR-2 appeared to be slightly superior to endothelial α v ß 3 for differentiating benign from cancerous lesions.
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.|Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Josef
authors.initials: J
authors.lastname: Ehling
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Misiewicz
authors.affiliation: Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: von Stillfried
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Möckel
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Bzyl
authors.affiliation: Bracco Suisse SA, Geneva, Switzerland.
authors.forename: Sibylle
authors.initials: S
authors.lastname: Pochon
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Wiltrud
authors.initials: W
authors.lastname: Lederle
authors.affiliation: Institute of Pathology, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knuechel
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.|Department of Targeted Therapeutics, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands.|Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Moritz
authors.initials: M
authors.lastname: Palmowski
authors.affiliation: Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen University, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Kiessling
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008875:Middle Aged; D015203:Reproducibility of Results; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D039302:Integrin alphaVbeta3; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: BR55; Breast cancer screening; Mammography; Molecular imaging; RGD