VEGF-A-independent and angiogenesis-dependent tumour growth in patients with metastatic breast cancer

• Autores: Xuan Bich Trinh, Peter A. van Dam, Peter B. Vermeulen, Steven J. Van Laere, Gert G. Van den Eynden, Wiebren A. A. Tjalma, Luc Y. Dirix
• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 13, Nº. 11, 2011, págs. 805-808
• Idioma: inglés
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• 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.