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. 2021 Sep 10;13(18):4539.
doi: 10.3390/cancers13184539.

Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology

Abraham Tsitlakidis  1 , Anastasia S Tsingotjidou  2 , Aristeidis Kritis  3 , Angeliki Cheva  4 , Panagiotis Selviaridis  1 , Elias C Aifantis  5 , Nicolas Foroglou  1
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Atomic Force Microscope Nanoindentation Analysis of Diffuse Astrocytic Tumor Elasticity: Relation with Tumor Histopathology

Abraham Tsitlakidis et al. Cancers (Basel). .

Abstract

This study aims to investigate the influence of isocitrate dehydrogenase gene family (IDH) mutations, World Health Organization (WHO) grade, and mechanical preconditioning on glioma and adjacent brain elasticity through standard monotonic and repetitive atomic force microscope (AFM) nanoindentation. The elastic modulus was measured ex vivo on fresh tissue specimens acquired during craniotomy from the tumor and the peritumoral white matter of 16 diffuse glioma patients. Linear mixed-effects models examined the impact of tumor traits and preconditioning on tissue elasticity. Tissues from IDH-mutant cases were stiffer than those from IDH-wildtype ones among anaplastic astrocytoma patients (p = 0.0496) but of similar elasticity to IDH-wildtype cases for diffuse astrocytoma patients (p = 0.480). The tumor was found to be non-significantly softer than white matter in anaplastic astrocytomas (p = 0.070), but of similar elasticity to adjacent brain in diffuse astrocytomas (p = 0.492) and glioblastomas (p = 0.593). During repetitive indentation, both tumor (p = 0.002) and white matter (p = 0.003) showed initial stiffening followed by softening. Stiffening was fully reversed in white matter (p = 0.942) and partially reversed in tumor (p = 0.015). Tissue elasticity comprises a phenotypic characteristic closely related to glioma histopathology. Heterogeneity between patients should be further explored.

Keywords: IDH; WHO grade; atomic force microscopy; diffuse glioma; elastic modulus; tissue mechanics.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The interaction effect between IDH mutation status and WHO grade on the elastic modulus E in the monotonic indentation model. IDH, isocitrate dehydrogenase gene family; WHO, World Health Organization.
Figure 2
Figure 2
The interaction effect between tissue type and WHO grade on the elastic modulus E in the monotonic indentation model. IDH-wildtype.
Figure 3
Figure 3
The interaction effect between tissue type and repetition on the elastic modulus E in the repetitive indentation model.
See this image and copyright information in PMC

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