The morphology of perinecrotic tumor cell nuclei in glioblastomas shows a significant relationship with survival time

Abstract

A deeper knowledge about histopathological criteria with a significant impact on the prognosis of patients with glioblastomas is worthwhile, since these patients may show a considerable difference in the time of survival. Investigation of the morphology of perinecrotic tumor cell nuclei is a promising approach, because the expression of specific molecules in these cells has been associated with a more aggressive behaviour of the tumors. In our series of patients with documented clinical course, 11 patients had a survival of at least 24 months and we compared this group with a group of 10 patients with maximum survival of 12 months. Digital microscopic image analysis was performed in paraffin sections from the primary surgical specimen. Three hundred perinecrotic tumor cell nuclei per case and 300 nuclei per case from tumor cells lying more distant from the tumor necroses ('distant zone' nuclei) were measured. The ratio for the numerical nuclear density between both types of nuclei was significantly larger in cases with short survival indicating a more pronounced nuclear density of perinecrotic nuclei in relation to the 'distant zone' nuclei in these tumors. In cases with long survival, on the contrary, perinecrotic tumor cells exhibited an only slightly larger numerical density compared with 'distant zone' nuclei. Mean values and standard deviations from parameters of nuclear shape (Fourier-amplitudes) had significantly smaller values in short-time survivors indicating a tendency towards a more circular nuclear shape with less pronounced intratumoral variation in that group. Based on the morphometric results, all cases could be correctly reclassified as short-or long-time survivors by means of cross-validated discriminant analysis. In conclusion, the results confirm significant morphological differences between tumors from patients with short and with long survival regarding morphology of both types of tumor cell nuclei. It seems likely, that histomorphometry of tumor cell nuclei could be a promising approach for the assessment of the individual prognosis of patients with glioblastomas.

Apoptosis induction in human glioblastoma multiforme T98G cells upon temozolomide and quercetin treatment

“…Histomorphometry of tumour cell nuclei could also be a promising approach for estimation of the prognosis for individual patients. It was shown that the nuclei had a tendency toward a more circular shape in short survivors [22, 23]. …”

“…For the analysis of the nuclear shape in the control and drug-treated cells, the roundness factor was used [22, 23] with value 1 for a circle and smaller values for increasing irregularities of nuclear shape. For visualisation of the nucleus, the cells were stained with Hoechst 33342 at a final concentration of 80 μg/ml for 5 min.…”

Long Term Survival in Patients Suffering from Glio-blastoma Multiforme: A Single-Center Observational Cohort Study

“…A limited number of investigations paid attention to the possible prognostic value of cytological and histological features. Nafe et al reported that the main cytological difference between STS and LTS is the increase of the nuclear density in necrotic areas of the lesions, resulting in a reduction in the internuclear distance in STS patients [40]. Finally the role of Ki67, the number of mitosis and extent of necrosis as a negative prognostic value is uncertain [18,40].…”

Automated nuclei clump splitting by combining local concavity orientation and graph partitioning

“…One approach to assigning cystosolic areas to individual cells it to start with the segmentation of cell nuclei. Furthermore, the morphology of nuclei is also commonly used as an indicator for various cellular states, such as apoptosis or necrosis [1], [2] and can represent important phenotypic features in classifying the effect of toxins or evaluating the longevity of the cells.…”

“…Specifically, it has been suggested that mitochondria in neurons from PD animal models undergo significant changes in mitochondrial membrane potential [6]. In order to study potential tipping points between healthy and diseased cellular states, it is crucial to study single cells and to analyze single cell variation over time in order to 1 Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg 2 National Center for Microscopy & Imaging Research, University of California, San Diego catch rare events in mitochondrial membrane potential [7], [8]. HeLa cells have a tendency to grow in monolayers due to the nature of 2D cell culture conditions.…”