Grading of diffusely infiltrating astrocytomas by quantitative histopathology, cell proliferation and image cytometric DNA analysis

Abstract

The aim of the study was to evaluate the applicability of quantitative histopathology as an aid for grading diffusely infiltrating astrocytomas. Primary astrocytomas were analysed for parameters (mean nuclear size, mitosis count, area fraction of endothelial cells and tumour necrosis, area fraction of nuclei, and Ki-67 (MIB-1) labelling index), which are closely related to the World Health Organization (WHO) 1979 and WHO 1993 grading criteria. All estimates correlated with the WHO histopathological grade and patient outcome. According to the receiver-operating characteristics curve, the presence of tumour necrosis and mitosis count (cut-off at 3 mitoses/mm2 of neoplastic tissue) showed the best sensitivity and specificity in separating patients with different survival. The multivariate survival analyses confirmed this result. A decision-tree model was constructed based on these two variables: twig I with less than 3 mitoses/mm2, twig II with equal or more than 3 mitoses/mm2 but no necrosis, and twig III with tumour necrosis. This model was found to be more strongly associated with survival than the WHO 1979 or WHO 1993 grading schemes. Low-malignancy astrocytomas (WHO grade II or twig I tumours) could be further divided into two prognostic categories by the image cytometric DNA analysis. The results put an emphasis on astrocytoma grading on mitosis counts (grade II vs. III) and tumour necrosis (grade III vs. IV). To standardize the sampling for mitosis counting, it is suggested that a parallel Ki-67 immunostaining be used for the identification of the most proliferative areas.

A Methodological Approach to the Characterization of Brain Gliomas, by Means of Semi-Automatic Morphometric Analysis

“…In other words, these astrocytic cells are more non-circular than pure oligodendrioma (O) ones. These findings are consistent with previous histopathological observations (Dymecki and Kulczycki 2005;Cooper et al, 2010) and with other morphometric studies of this family of neoplasmas, providing further confirmation of the good quality of the results obtained (Nafe et al, 2000;Sallinen et al, 2000). It is interesting that astrocytoma tumors show an increase in AR with increasing malignancy grade (from II-nd [i.e., ADm] to III-rd [i.e.…”

“…This allows a description of selected features of glioma cellular nuclei, due to the relatively sharp contrast between cell nuclei and surrounding tissue. In order to perform densitometry analysis Fuelgen staining (showing the cellular nuclei DNA content) (Cruz-Sánchez et al, 1997) and various kinds of immunohistochemical staining are also applied in neuro-oncological histomorphometric investigations (Ricco et al, 1994;Sallinen et al, 2000).…”

Revisiting anaplastic astrocytomas I: An expansive growth pattern is associated with a better prognosis

“…The crucial distinction between grade II and grade III astrocytomas is based on the detection of mitoses. A solitary mitosis is often found only after a thorough and often tedious search through multiple permanent sections (25). Giannini et al (20) found that the prognosis of grade III tumors with solitary mitosis resembled that of grade II tumors.…”

Expression and distribution of id helix‐loop‐helix proteins in human astrocytic tumors

“…Antbodies (Ab) against glial fibrillary acidic protein (GFAP; polyclonal rabbit; Dako, Denmark; 1: 2,000) and vimentin (mouse clone V9; Dako; 1:25) were used (Sallinen et al, 2000). To detect Id proteins, we used specific rabbit anti-human Id1, Id2, and Id3 polyclonal antibodies (Santa Cruz Biotechnology, CA).…”