Grading of diffusely infiltrating astrocytomas by quantitative histopathology, cell proliferation and image cytometric DNA analysis - Comparison of 133 tumours in the context of the WHO 1979 and WHO 1993 grading schemes

The aim of the study was to evaluate the applicability of quantitative hist opathology as an aid for grading diffusely infiltrating astrocytomas. Prima ry astrocytomas were analysed for parameters (mean nuclear size, mitosis co unt, 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. Al l estimates correlated with the WHO histopathological grade and patient out come. According to the receiver-operating characteristics curve, the presen ce of tumour necrosis and mitosis count (cut-off at 3 mitoses/mm(2) of neop lastic tissue) showed the best sensitivity and specificity in separating pa tients with different survival. The multivariate survival analyses confirme d this result. A decision-tree model was constructed based on these two var iables: twig I with less than 3 mitoses/mm(2), twig II with equal or more t han 3 mitoses/mm(2) but no necrosis, and twig III with tumour necrosis. Thi s model was found to be more strongly associated with survival than the WHO 1979 or WHO 1993 grading schemes. Low-malignancy astrocytomas (WHO grade I I or twig I tumours) could be further divided into two prognostic categorie s by the image cytometric DNA analysis. The results put an emphasis on astr ocytoma grading on mitosis counts (grade II vs. III) and tumour necrosis (g rade III vs. IV). To standardize the sampling for mitosis counting, it is s uggested that a parallel Ki-67 immunostaining be used for the identificatio n of the most proliferative areas.