Variability in the proliferative potential of human gliomas

Hoshino, Takao; Nagashima, Tadashi; Cho, Kyung G.; Davis, Richard L.; Donegan, Judith H.; Slusarz, Maureen; Wilson, Charles B.

doi:10.1007/bf00165098

Cited by 35 publications

(9 citation statements)

References 15 publications

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“…Infiltration, anaplasia, and recurrences of tumors are linked to There is increasing evidence that the LI carries clinical significance, the higher the LI the more ominous the prognosis. 6 -7 ' 39 The course of a brain tumor is influenced by multiple factors such as size, location, age, degree of edema, necrosis, 7 vascularity, 7 and invasiveness. 40 Nevertheless, the cellular proliferative potential, determined by Ki-67 immunohistochemistry, should be added to the armamentarium of the neuropathologist in the routine assessment of surgical material to provide dynamic cytokinetic data that will complement classical histopathologic diagnosis based upon morphology alone.…”

Section: Discussionmentioning

confidence: 99%

The Cycling Pool of Cells within Human Brain Tumors:In SituCytokinetics Using the Monoclonal Antibody Ki-67

Tsanaclis¹,

Robert²,

Michaud³

et al. 1991

Can. j. neurol. sci.

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Brain tumor growth results from the relative proportion of cells contained in three populations: a) cycling/proliferative; b) quiescent (G 0 )/static, and c) terminally differentiated/dying. The cycling compartment can be detected by the mouse monoclonal Ki-67 antibody, an available, rapid, safe, sensitive, and specific method for immunostaining of proliferative cells. We report the Ki-67 labeling index (LI) in 48 brain tumors. Malignant brain tumors have elevated Lis, ranging from 6.0% to 56.9%: anaplastic astrocytoma, 8.0 ± 7.3; glioblastoma multiforme, 10.1 ±4.2; germinoma, 11.7; medulloblastoma, 13.1 ±6.6; metastases, 40.3 ± 13.1. By contrast, slow-growing tumors showed lower values (P < .001), approaching 1%: acoustic schwannoma, 0.4 ± 0.6; pituitary adenoma, 1.3 ± 1.9; meningioma, 1.2 ± 1.2; low-grade astrocytoma, < 1; pilocytic astrocytoma, 5.6. Human brain tumors can therefore be ranked according to the percentage of cycling cells with the acoustic schwannoma among the least proliferative and the metastatic carcinoma among the most proliferative. Within a given histotype, the Ki-67 LI may have prognostic and therapeutic implications for the individual patient. Already important for neuro-oncology research, the Ki-67 labeling index should be added to the armamentarium of the clinical neuropathologist to complement the standard histopathologic diagnosis with a cytokinetic analysis of cellular proliferation. RESUME: La proportion de cellules en proliferation dans les tumeurs cerebrales humaines: analyse cytokinetique in situ avec I'anticorps monoclonal Ki-67. La croissance d'une tumeur est le resultat de la proportion relative de trois populations cellulaires: a) en phase proliferative, b) quiescente (G 0 ) et c) completement differenciees. Le compartiment des cellules en proliferation peut etre evalue par immunocytochimie avec I'anticorps monoclonal Ki-67; cette m6thode est facile, rapide et specifique. Nous decrivons l'index de marquage (I.M.) obtenu sur 48 tumeurs c6r6brales provenant de 47 malades operes. Pour les tumeurs malignes 1'I.M. s'est avere" tres eleve, avec des valeurs limites entre 6.0% et 56.9%: 8.0 ± 7.3 pour l'astrocytome anaplasique; 10.1 ± 4.2 pour le glioblastome multiforme; 11.7 pour le germinome; 13.1 ± 6.6 pour le medulloblastome et 40.3 ± 13.1 pour les metastases. Par contre, pour les tumeurs a croissance lente 1'I.M. (P < .001) tourne autour de 1%: 0.4 ± 0.6 pour le schwannome du VIII nerf; 1.3 ± 1.9 pour I'adenome hypophysaire; 1.2 ± 1.2 pour le meningiome; <1 pour l'astrocytome benin; 5.6 pour l'astrocytome pilocytique du cervelet. Les tumeurs cerebrales humaines peuvent etre classees selon le pourcentage de cellules en proliferation: les schwannomes ont les valeurs les plus faibles tandis que les metastases ont les chiffres les plus Sieves. Dans une meme tumeur 1'I.M. evalue par le Ki-67 peut avoir des implications pronostiques et therapeutiques pour un malade en particulier. Cette methode deja importante pour la recherche en neuro-oncologie, devra etre incoporee dans ...

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Section: Discussionmentioning

confidence: 99%

The Cycling Pool of Cells within Human Brain Tumors:In SituCytokinetics Using the Monoclonal Antibody Ki-67

Tsanaclis¹,

Robert²,

Michaud³

et al. 1991

Can. j. neurol. sci.

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“…Our data suggest that younger patients with mixed gliomas have a shorter time to recurrence than older patients; however, this finding was of modest statistical significance. In astrocytic tumors, the BrdU LI has been shown to correlate with age [23][24][25]. In this series, all patients who were recurrence-free for more than 24 months after their initial operation were less than 50 years of age at the time of diagnosis and had BrdU LI's _< 3.0%.…”

Section: ]mentioning

confidence: 93%

“…Younger patients with astrocytoma have a much better prognosis than older patients [22][23][24]. The generally young age of patients with mixed gliomas is thought to play a role in their longer survival.…”

Section: ]mentioning

confidence: 97%

The prognostic implications of histologic classification and bromodeoxyuridine labeling index of mixed gliomas

et al. 1994

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To clarify the biological and clinical behavior and prognosis of mixed gliomas, 47 patients underwent intraoperative bromodeoxyuridine (BrdU) labeling studies. The mean age was 27.8 years at symptom onset and 31.8 years at labeling (median, 36 years). Forty-five tumors were supratentorial, 30 were frontal, and two were cerebellar; 16 were recurrent at labeling. The median labeling index (LI) was 1% (range, < 1 to 15.1%). Forty-six tumors has oligodendroglial and astrocytic elements, and one had astrocytic and ependymal elements. The median LI was 4.4% in recurrent tumors and < 1% in primary tumors. A higher BrdU LI correlated with an increased risk of recurrence and a shorter time to recurrence. During a median follow-up of 16 months, four patients died; each had a BrdU LI > or = 4.4%. The median time to recurrence was 4.5 months for tumors with BrdU LI's > 5% but was not reached for tumors with LI's < 5% (p < 0.003). The histologic grade of the oligodendroglial component correlated with the median time to recurrence (8 months for Smith Grade C tumors, not reached for Smith Grade B tumors; p < 0.05); there were too few cases to evaluate the median times to recurrence of Smith Grade A and Grade D tumors. The median time to recurrence was not reached for any astrocytic grade, and there were no significant differences in the Kaplan-Meier survival curves. These findings suggest that the BrdU LI and the grade of the oligodendroglial component of mixed gliomas have prognostic significance.

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“…Final administrations were performed 1 h before the acquisition trial in the passive avoidance task. Independently of behavioral studies, BrdU, a thymidine analog, which incorporates into the DNA of dividing cells during the S phase of the cell cycle, was used to label dividing cells (Hoshino et al, 1989;Struikmans et al, 1997). BrdU (50 mg/kg, i.p.)…”

Section: Drug Administrationmentioning

confidence: 99%