title: High-grade glioma before and after treatment with radiation and Avastin: initial observations.
abstract: 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.
authors.affiliation: Department of Pathology, New York University Medical Center, New York, NY, USA. ifischer@mdanderson.org
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Fischer
authors.forename: Clare H
authors.initials: CH
authors.lastname: Cunliffe
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Bollo
authors.forename: Shahzad
authors.initials: S
authors.lastname: Raza
authors.forename: David
authors.initials: D
authors.lastname: Monoky
authors.forename: Luis
authors.initials: L
authors.lastname: Chiriboga
authors.forename: Erik C
authors.initials: EC
authors.lastname: Parker
authors.forename: John G
authors.initials: JG
authors.lastname: Golfinos
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Kelly
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Knopp
authors.forename: Michael L
authors.initials: ML
authors.lastname: Gruber
authors.forename: David
authors.initials: D
authors.lastname: Zagzag
authors.forename: Ashwatha
authors.initials: A
authors.lastname: Narayana
mesh_terms: D000199:Actins / Q000187:drug effects / Q000528:radiation effects; D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34 / Q000187:drug effects / Q000528:radiation effects; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D002352:Carrier Proteins / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008840:Microfilament Proteins / Q000187:drug effects / Q000528:radiation effects; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000199:Actins; D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018952:Antigens, CD34; D002352:Carrier Proteins; D008840:Microfilament Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C020324:fascin; D000068258:Bevacizumab