Histological grading, DNA content, cell proliferation and survival of patients with astroglial tumors

Zaprianov, Z; Christov, Konstantin

doi:10.1002/cyto.990090416

Cited by 40 publications

(9 citation statements)

References 17 publications

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“…This is in agreement with other studies using semiquantitative scoring of mitotic number [5][6][7]. DNA-indices also correlates with the survival pattern [29]. DNA-ploidy level, number of Ki-67 positive tumor cells, and BUdR labelling index show correlation to morphological grade of malignancy [28][29].…”

Section: Discussionsupporting

confidence: 92%

Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors Practical technique and use in prognostic evaluation

Sørensen¹,

Brændgaard

Chistiansen

et al. 1991

J Neuro-Oncol

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The use of morphometry and modern stereology in malignancy grading of brain tumors is only poorly investigated. The aim of this study was to present these quantitative methods. A retrospective feasibility study of 46 patients with supratentorial brain tumors was carried out to demonstrate the practical technique. The continuous variables were correlated with the subjective, qualitative WHO classification of brain tumors, and the prognostic value of the parameters was assessed. Well differentiated astrocytomas (n = 14) had smaller estimates of the volume-weighted mean nuclear volume and mean nuclear profile area, than those of anaplastic astrocytomas (n = 13) (2p = 3.1.10(-3) and 2p = 4.8.10(-3), respectively). No differences were seen between the latter type of tumor and glioblastomas (n = 19). The nuclear index was of the same magnitude in all three tumor types, whereas the mitotic index was significantly increased in glioblastomas (2p = 0.01). Three-dimensional, shape-independent estimates of macroscopical tumor volume were not different in anaplastic astrocytomas and glioblastomas (2p = 0.39). Histological type of tumor and mitotic index were of significant prognostic value (2p = 8.2.10(-6) and 2p approximately 0.05, respectively). Age above the median and short duration of symptoms were significantly associated with short survival (2p = 0.01). Further investigations of larger series of patients are needed to define the clinical usefulness of these objective, reproducible, and quantitative techniques in the prognostic evaluation of primary brain tumors.

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Section: Discussionsupporting

confidence: 92%

Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors Practical technique and use in prognostic evaluation

Sørensen¹,

Brændgaard

Chistiansen

et al. 1991

J Neuro-Oncol

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“…The diagnostic accuracy in histopathological grading of astrocytomas depends largely on the experience of the observer, and much effort has been put on objective prognostic characterization of the tumours [2±5,7,9±11,14±16, 19,21,22,24,25,28,30]. The pre- sent study evaluated whether quantitative assessment by computer-assisted techniques could aid the interpretation of the established WHO 1993 grading criteria.…”

Section: Introductionmentioning

confidence: 99%

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

Sallinen

Helén³

et al. 2000

Neuropathology Appl Neurobio

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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.

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“…Human brain tumors have been studied repeatedly by FCM (Hoshino et al, 1978;Frederiksen et al, 1978;Mork and Laerum, 1980;Borchers and Beck, 1980) and most studies indicate that FCM aneuploidy prevails in poorly differentiated tumors (Danova et al, 1986a;Ahyal, 1988;Onda et al, 1988;Spaar and Spaar, 1990). The correlation between FCM DNA content and clinical behavior has been addressed only in a few studies, generally containing a limited number of cases analyzed by univariate analysis, which give contradictory results (Danova et al, 1987a;Zaprianov and Christov, 1988;Jimenez et al, 1989;Coons et al, 1990). In view of such conflicting results, we have performed a multivariate analysis of DNA-ploidy and patient survival in a large number of patients with neuroepithelial tumors, while controlling for histologic subtype, sex and age and anatomical tumor location.…”

mentioning

confidence: 99%

Prognostic significance of nuclear DNA content in human neuroepithelial tumors

Danova¹,

Giaretti²,

Merlo³

et al. 1991

Intl Journal of Cancer

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The relationship between survival and flow cytometric DNA-ploidy and other prognostic factors such as histological subtype, anatomical tumor site, patient sex and age was investigated in 153 patients with intracranial neuroepithelial tumors who underwent surgical treatment. We found a trend toward poorer survival from anaplastic astrocytomas and glioblastomas with respect to low-grade (I and II) astrocytomas (which did not differ significantly); accordingly, patients were grouped into these 3 histologic subgroups. Thirty-seven of the 153 tumors (24.2%) were aneuploid with a median DNA-index (DI) of 1.3 (range: 1.2-2.0). DNA-ploidy correlated with histology, since anaplastic astrocytomas and glioblastomas were significantly (p = 0.041) more frequently aneuploid (around 30%) than low-grade astrocytomas (around 10%). Patients with DNA-aneuploid tumors (i.e., with DI not equal to 1.00) survived for a shorter time (31.4 weeks) than patients with DNA diploid tumors (75.1 weeks) (p less than 0.001). This difference was confirmed by Cox's multivariate analysis. Aneuploid tumors were associated with a poorer survival (p = .0002) when compared with diploid tumors, resulting in a relative risk point estimate (RR) of 2.41, 95% confidence interval (Cl) = 1.55-3.74. Histological subtype was also significantly associated with survival (p less than 0.0001), with RRs of 2.09, 95% Cl = 1.13-3.86 and 3.59, 95% Cl = 1.96-6.59 for anaplastic astrocytomas and glioblastomas, respectively, compared to low-grade astrocytomas. We therefore suggest that the flow cytometric measurement of DNA-ploidy has relevant significance in predicting survival in patients treated for intracranial neuroepithelial tumors.

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Histological grading, DNA content, cell proliferation and survival of patients with astroglial tumors

Cited by 40 publications

References 17 publications

Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors Practical technique and use in prognostic evaluation

Stereological estimates of nuclear volume and other quantitative variables in supratentorial brain tumors Practical technique and use in prognostic evaluation

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

Prognostic significance of nuclear DNA content in human neuroepithelial tumors

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