title: Expression of Heat Shock Protein 27 in Melanoma Metastases Is Associated with Overall Response to Bevacizumab Monotherapy: Analyses of Predictive Markers in a Clinical Phase II Study.
abstract: The aim of this study was to identify potential predictive biomarkers in 35 patients with metastatic melanoma treated with anti-angiogenic bevacizumab monotherapy in a clinical phase II study. The immunohistochemical expression of various angiogenic factors in tissues from primary melanomas and metastases as well as their concentration in blood samples were examined. Strong expression of Heat Shock Protein 27 (HSP27) in metastases correlated significantly with complete or partial response to bevacizumab (p = 0.044). Furthermore, clinical benefit, i.e., complete or partial response or stable disease for at least 6 months, was more frequent in patients with strong expression of HSP27 in primary tumors (p = 0.046). Tissue expression of vascular endothelial growth factor (VEGF-A), its splicing variant VEGF165b or basic fibroblast growth factor (bFGF) did not correlate with response, and the concentration of HSP27, VEGF-A or bFGF measured in blood samples before treatment did not show predictive value. Further, microvessel density, proliferating microvessel density and presence of glomeruloid microvascular proliferations were assessed in sections of primary tumors and metastases. Microvessel density in primary melanomas was significantly higher in patients with clinical benefit than in non-responders (p = 0.042). In conclusion, our findings suggest that strong HSP27 expression in melanoma metastases predicts response to bevacizumab treatment.
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schuster
authors.affiliation: Centre for Cancer Biomarkers CCBIO, Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: Lars A
authors.initials: LA
authors.lastname: Akslen
authors.affiliation: Department of Oncology and Medical Physics, Haukeland University Hospital, Bergen, Norway.|Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Oddbjørn
authors.initials: O
authors.lastname: Straume
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D055551:HSP27 Heat-Shock Proteins / Q000097:blood / Q000235:genetics*; D006360:Heat-Shock Proteins; D006801:Humans; D008113:Liver Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D018832:Molecular Chaperones; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D011379:Prognosis; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000235:genetics
chemical_list: D020533:Angiogenesis Inhibitors; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000068258:Bevacizumab