Download 1 Diplomarbeitsthema Histo-morphometric analysis of a

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Diplomarbeitsthema
Histo-morphometric analysis of angioarchitecture in low-grade gliomas on 2D high-resolution
digital images
Collaborators:
Medical University of Vienna:
Matthias Preusser, MD
Department of Internal Medicine I/Oncology
Johannes A. Hainfellner, MD
Institute of Neurology
Harald Heinzl, PhD
Core Unit for Medical Statistics and Informatics, Section of Clinical Biometrics
Adelheid Woehrer, MD
Medical University of Vienna
Institute of Neurology
Georg Widhalm, MD
Department of Neurosurgery
Vienna University of Technology:
Wolfgang Wertz
Matthias Templ, ...
...
Frank Rattay, ...
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Cornelia Wenger, ...
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Background
Low-grade gliomas (LGG) including diffuse astrocytoma, oligoastrocytoma and oligodendroglioma are
rare brain neoplasms most commonly affecting adults [1]. LGG show diffuse growth in the brain
parenchyma and invariably recur or progress to high-grade glioma. Most cases of LGG lead to patient
death with survival times ranging from approximately 5-15 years [1].
By definition, at histopathological analysis LGG lack glomeruloid and layered endothelial proliferates
typically found in high-grade glioma [1]. However, LGG show considerable variability in
vascularization between cases (Figure 1). Little is known about patterns of angioarchitecture and
their clinical relevance in LGG. Methods commonly used for assessment of tumor vascularization
including analysis of hot-spot microvessel density (MVD) have substantial methodological limitations
(low interobserver reproducibility) and seem inadequate to describe the irregular geometry of tumor
angioarchitecture [2].
Histo-morphometric analysis of tumor vascularization may more adequately capture the complex
architecture by considering the number of vessels, the variability in vessel shapes and sizes and the
pattern of vessel distribution within a tumor specimen.
Aim of the study
The aim of the present study is to develop a reliable algorithm for computer-assisted objective
assessment of LGG angioarchitecture.
Methods
The study will be performed on formalin-fixed and paraffin-embedded tumour tissue specimens from
20 LGG patients treated at the Medical University of Vienna. Of each tissue specimen,
immunohistochemical staining for CD34 antigen will be performed to visualize intratumoural
microvessels. All immunostained slides will be scanned and the high resolution 2D digital slides will
be stored for further data processing.
Algorithms that yield objective indicators of tumour vascularization on the 2D images will be defined
after critical appraisal of available mathematics and informatics tools, and consensual agreement
achieved between the experts in medicine and mathematics/statistics/informatics.
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Outlook
If this project succeeds in development of an algorithm for objective assessment of LGG
angioarchitecture on 2D high resolution digital images, the reproducibility and clinical relevance will
be tested in EORTC study 22033-26033, a large, multicenter, prospective, randomized clinical phase
III trial investigating the effect of primary chemotherapy with temozolomide versus radiotherapy in
patients with low grade gliomas. Adult patients with histologically proven supratentorial LGG are
eligible and chromosome arm 1p deletion status will be included as stratification factor. Of each
patient enrolled in the trial, formalin-fixed and paraffin-embedded (FFPE) tumor tissue specimens are
being collected in a central pathology laboratory (Erasmus University Hospital, Rotterdam, the
Netherlands). As of August 2009, 354 of 466 required patients have been randomized.
Randomization of the last patient is expected for late 2010.
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References
1.
Louis DN, Ohgaki H, Wiestler OD, Cavanee WK: WHO Classification of Tumours of the Central
Nervous System. IARC Press, Lyon, 2007
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Preusser M, Heinzl H, Gelpi E, Schonegger K, Haberler C, Birner P, Marosi C, Hegi M, Gorlia T,
Hainfellner JA (2006) Histopathologic assessment of hot-spot microvessel density and vascular
patterns in glioblastoma: Poor observer agreement limits clinical utility as prognostic factors: a
translational research project of the European Organization for Research and Treatment of Cancer
Brain Tumor Group. Cancer 107:162-170.
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Legend to Figure 1. The vascularization is variable between low-grade-glioma (LGG) cases.
A. Exemplary case of LGG showing delicate and evenly distributed microvessels.
B. Exemplary case of LGG showing delicate clusters of irregularly shaped microvessels. Glomeruloid
and layered endothelial proliferates typical for high grade glioma are lacking.
A and B: Anti-CD34 immunohistochemistry; brown signals: endothelial cells, blue signals: tumour cell
nuclei.