Histology far away from Flatland: 3D roller-coasting into grade-dependent angiogenetic patterns in oligodendrogliomas

Abstract

Angiogenesis plays a key role in tumour progression, and undergoes structural changes associated to tumour biology itself. Although vessel density can be easily evaluated in brain tumours using a traditional immuno-histochemical approach, other parameters of conceptual/biological interest, such as the complex patterns of vascular growth, cannot be fully understood using a traditional bi-dimensional evaluation. We use here surgical specimens derived from oligodendrogliomas as a model for a novel elucidative 3D reconstruction of the grade-dependent vascular arborisation in brain tumours.

1

Progressive 3D vessel reconstruction. Forty serial sections of a grade II oligodendroglioma were stained using an anti-CD34 antibody (A) in order to recognize the vascular structures. A sequential (B–L) automated analysis and reconstruction of the different layers allowed a final 3D informative image of the complex vascular system unrolling within the tumour.

2

Vascular architecture in grade II oligodendroglioma. The 3D reconstruction in a case of oligodendroglioma grade II demonstrated an angiogenetic process mainly based on a sprouting/branching architecture (A, B). The vessels are finely interconnected each other and the peripheral areas display numerous small structures without any connection with the main vessels which could represent the initial instable expression of an ‘angiogenesis in progress’ process (arrows).

3

3D reconstruction of vascular architecture in a grade III oligodendroglioma. The 2D immunohisto-chemistry-based evidence of the grade III oligodendroglioma vascula-ture shows vessel of variable diameter strictly interconnected (A). Such image is fully elucidated and completed by the 3D reconstruction, in which the vascular tree exhibits a larger diameter compared to grade II tumours with thickly bundled vessels (B–E). The arrow heads indicate different areas of blood wall invagination possibly due to intussusception process.