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This Article Full Text Full Text (PDF) All Versions of this Article: 10/5/700    most recent 15228517-2008-042v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fischer, I. Articles by Narayana, A. Search for Related Content PubMed PubMed Citation

High-grade glioma before and after treatment with radiation and Avastin: Initial observations

Departments of Pathology (I.F., C.H.C., L.C., D.Z.), Neurosurgery (R.J.B., E.C.P., J.G.G., P.J.K.), Radiology (D.M., E.A.K.), Oncology (M.L.G.), and Radiation Oncology (S.R., A.N.), New York University Medical Center, New York, NY, USA

Address correspondence to Ingeborg Fischer, The University of Texas MD Anderson Cancer Center, Department of Pathology, 1515 Holcombe Blvd., Houston, TX 77030, USA (ifischer{at}mdanderson.org).

We evaluate the effects of adjuvant treatment with the angiogenesis inhibitor Avastin (bevacizumab) on pathological tissue specimens of high-grade glioma. Tissue from five patients before and after treatment with Avastin was subjected to histological evaluation and compared to four control cases of glioma before and after similar treatment protocols not including bevacizumab. Clinical and radiographic data were reviewed. Histological analysis focused on microvessel density and vascular morphology, and expression patterns of vascular endothelial growth factor–A (VEGF-A) and the hematopoietic stem cell, mesenchymal, and cell motility markers CD34, smooth muscle actin, D2-40, and fascin. All patients with a decrease in microvessel density had a radiographic response, whereas no response was seen in the patients with increased microvessel density. Vascular morphology showed apparent "normalization" after Avastin treatment in two cases, with thin-walled and evenly distributed vessels. VEGF-A expression in tumor cells was increased in two cases and decreased in three and did not correlate with treatment response. There was a trend toward a relative increase of CD34, smooth muscle actin, D2-40, and fascin immunostaining following treatment with Avastin. Specimens from four patients with recurrent malignant gliomas before and after adjuvant treatment (not including bevacizumab) had features dissimilar from our study cases. We conclude that a change in vascular morphology can be observed following antiangiogenic treatment. There seems to be no correlation between VEGF-A expression and clinical parameters. While the phenomena we describe may not be specific to Avastin, they demonstrate the potential of tissue-based analysis for the discovery of clinically relevant treatment response biomarkers.

Key Words: angiogenesis • Avastin • bevacizumab • biomarkers • glioblastoma • glioma

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