title: VEGF-A-independent and angiogenesis-dependent tumour growth in patients with metastatic breast cancer.
abstract: BACKGROUND The mechanisms of tumour progression during anti-VEGF-A treatment are poorly understood. PATIENTS AND MATERIALS Two patients with metastatic breast cancer are described who developed new metastases while receiving anti-VEGF-A treatment. Angiogenic parameters were determined by CD34/Ki67 double staining, Chalkley counts (CC) and endothelial cell proliferation fractions (ECP). RT-PCR Taqman low-density arrays with a gene panel of 94 angiogenesis-related genes were performed on both metastases and compared to 10 unselected primary breast tumours. RESULTS Both lesions showed a high and intermediate CC of, respectively, 7.5±0.62 and 4.8±0.2. Both lesions had elevated ECP values of 14% and 8%. Low-density array screening showed that VEGFR1 mRNA was overexpressed in both samples (z-score=7.85 and 7.81) compared to control samples (out of range [min-max]). Additional analysis confirmed this finding at the protein level by immunohistochemistry. CONCLUSION These observations suggest that tumour progression under continuous anti-VEGF-A continues to be angiogenesis dependent. Further exploration is needed to identify the mechanisms of anti-VEGF-A resistance in order to design combination-targeted therapies.
authors.affiliation: Translational Cancer Research Group-Antwerp, Oncology Centre, St. Augustinus Hospital, Wilrijk-Antwerp, Belgium.
authors.forename: X Bich
authors.initials: XB
authors.lastname: Trinh
authors.forename: P A
authors.initials: PA
authors.lastname: van Dam
authors.forename: P B
authors.initials: PB
authors.lastname: Vermeulen
authors.forename: S J
authors.initials: SJ
authors.lastname: Van Laere
authors.forename: G G
authors.initials: GG
authors.lastname: Van den Eynden
authors.forename: W A A
authors.initials: WA
authors.lastname: Tjalma
authors.forename: L Y
authors.initials: LY
authors.lastname: Dirix
mesh_terms: D001943:Breast Neoplasms / Q000098:blood supply / Q000473:pathology* / Q000628:therapy; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000628:therapy; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D040281:Vascular Endothelial Growth Factor Receptor-1
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