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Clin Transl Oncol ; 13(11): 805-8, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22082645

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/patología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/terapia , Proliferación Celular , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Neovascularización Patológica/genética , Neovascularización Patológica/terapia , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
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