Acta Neurochir (Wien) (2004) 146: 37–44

DOI 10.1007/s00701-003-0173-4

Clinico-Pathological StudyThe Ki-67 proliferation antigen in meningiomas. Experiencein 600 cases

F. Roser1, M. Samii1;2, H. Ostertag3, and M. Bellinzona1

1 Department of Neurosurgery, Klinikum Hannover Nordstadt, Hannover, Germany2 International Neuroscience Institute, Klinikum Hannover Nordstadt, Hannover, Germany3 Institute of Pathology, Klinikum Hannover Nordstadt, Hannover, Germany

Published online December 22, 2003

# Springer-Verlag 2003

Summary

Background. Meningiomas are mostly benign tumours that can be

cured by surgical resection. Because meningiomas tend to recur, long

term management in patients with subtotal tumour resection remains

controversial. Previous studies have shown that the proliferation poten-

tial of meningiomas by Ki-67 labelling indices (LI) might predict their

natural history. The purpose of this study was to analyse the reliability of

Ki-67-labelling index in predicting the behaviour of meningiomas, and

to help the neurosurgeon in establishing better follow up criteria and

long term management strategies for these patients.

Method. From 1990 to 2000 1328 meningiomas have been operated

in our Neurosurgical Department. A total of 600 tumours were examined

immunohistochemically using the Mib-1 monoclonal antibody. Clinical

charts of the patients including surgical, histological and follow up

records, as well as imaging studies were analysed retrospectively. Ki-

67 LI were correlated with neuroradiological findings, 3D volumetric

studies, histological subtype, recurrence-free survival, grade of resection,

consistency of tumour tissue, location, osseous involvement, en plaque

appearance, vascularity and progesterone-receptor status.

Findings. Among the 600 patients analysed, there were 66% females

(mean LI 3.8%) and 34% males (mean LI 5.7%), including 20 neurofi-

bromatosis-type-2 (NF-II) patients with a mean LI of 5.2%. Histological

grading revealed 91% WHO�I meningiomas (mean LI 3.28%), 7%

WHO�II (mean LI 9.95%) and 2% WHO�III (mean LI 12.18%). Label-

ling indices in recurrent meningiomas increased from initial resection to

a fourth local resection. A significant correlation between negative

progesteron-receptor status and high tumour vascularity with high Ki-

67 LI was seen. Ki67 was not a statistically significant predictor of

survival time in totally excised WHO�I meningiomas.

Interpretation. Mib-1 is one important tool in addition to routine

histological evaluation, but a combination of clinical factors and parti-

cularly the extent of surgical resection, along with the biological features

of the tumour, should influence the decision of the neurosurgeon to the

patient follow up.

Keywords: Meningioma; Mib-1; Ki-67; recurrence; proliferation.

Introduction

Although generally considered benign, the biological

behaviour of meningiomas varies considerably. Not only

histopathological criteria but also the surgical grade of

resection determines the recurrence free-survival in

patients with histologically comparable meningiomas

[3, 18, 34, 48]. Between 7 and 32% of benign menin-

giomas recur after total resection, and between 19 and

50% after subtotal removal [11, 20]. Because of

their clinical behaviour with a tendency to recur and

unfavourable outcome after repeated operations, menin-

giomas cannot be classified as a benign entity despite

their pathological classification. Decisions regarding

patient management therefore rely on a variety of clin-

ical, radiological and pathological prognosticators.

Growth potential of meningioma is variable and even

the microscopic morphological classification of the

World Health Organization (WHO) cannot predict the

clinical behaviour of these tumours [25]. Quantifying

their proliferative potential may help to predict the bio-

logical behaviour of individual tumours of comparable

histology. The prognostic significance of various pro-

liferative indices in meningiomas has already been

assessed by other authors, and it has been suggested that

the tumour proliferative potential can predict the

patient’s clinical course [1, 2, 11, 16, 20, 23, 28, 32,

33, 35, 40, 42, 44]. The nuclear antigen Ki-67 expressed

by proliferating cells has become available for routinely

processed paraffin section [8, 15]. The Mib-1 antibody

detects an epitope on the Ki-67 antigen, a nuclear pro-

tein present only during active phases of the cell cycle

(G1, S, G2 and M). Several studies were done to inves-

tigate how Ki-67 labelling indices could help to predict

recurrences. However, a lack of adequate case numbers,

inconsistent statistical methods and clinical considera-

tions precludes a comparison of these studies. The aim

of the present study was to assess if and how the neu-

rosurgeon can rely on the Ki-67 labelling index to use

the best follow-up criteria and therapeutic options.

Therefore we compared selected histopathological and

macroscopical features as well as survival times in me-

ningioma patients. Further comparisons were made for

each patient in the recurrent group between the initi-

ally resected tumour and all local recurrences to deter-

mine whether recurrent meningioma tends to become

histologically more aggressive.

Materials and methods

Between 1990 and 2000, 1328 meningiomas have been removed in

our Neurosurgical Department. Six hundred paraffin blocks of 554

patients were selected and the paraffin blocks retrieved from the

archives. Among our patients there were 184 males and 370 females

(ratio 1:2), ranging in age from 15 to 94 (mean age of 64). All patients

were followed for a median of 74 months (ranging from 3–228 months)

or until death. The material included 20 patients with NF-II disease

(for a total of 28 tumours), with a mean age of 32.3 years at presentation

(16–60) and a male to female ratio of 1:1. Clinical information of each

patient was obtained through review of medical records, as well as

follow-up examinations with clinical and neuroradiological evaluation

or through detailed questionnaires with radiological reports of the latest

MRI findings.

Paraffin sections were stained with hematoxylin-eosin, and neoplastic

areas were delineated. They were categorized into meningioma subtypes

according to the new WHO classification [25]. Immunohistochemistry

was performed using 2mm thick paraffin sections. In short, paraffin sec-

tions were dewaxed and stained with Anti-Mib-1 purchased from DAKO

[Copenhagen, Denmark], according to standard protocols using the

ChemMate Detection Kit Alkaline Phospatase from DAKO [Copenhagen,

Denmark] and NeoFuchsin as chromogen. Sections were counterstained

with Hemalaun and coverslipped with KP tape [KliniPath BV, Nether-

lands]. Positive control specimens were run in every essay using glioblas-

toma tissue. Also, negative controls were run in every staining session.

In each case, the entire section was systematically examined using an

optical grid on high power fields (400� , ZEISS microscope) for the

presence of immunoreactivity. In every slide the area of densest staining

(‘hot spot’), was searched for and counting was performed in 10 contig-

uous fields. The average of the results in these fields determined the

proliferative index (LI). Only unquestionably stained nuclei were accepted

as positively stained. All slides were routinely examined by one patholo-

gist (HO). Randomly chosen stains were also counted by independent

researchers to check the interindividual difference of interpretation of the

mean Ki-67 LI, and revealed no statistically significant differences.

Statistical analysis was performed using the SPSS 10.0 (SPSS Inc.)

software program for windows. Several parameters shown in the result

section were analysed with Student’s t-test or log-rank tests. Mean value,

standard deviation (SD) and P-value were calculated. Differences were

considered significant at P-value <0.05. The distribution of the re-

currence-free survival times were estimated using the Kaplan-Meier

method. Pearson’s regression analysis was performed to determine the

correlation between mean Ki-67 LI and other influencing factors. Multi-

variate analysis (ANOVA) was also performed. Volume measurements

were performed with the Image J program (Scion Image, based on NIH

Image. Beta Release 4.0.2) scanning adjacent axial, coronal and sagittal

slices of post contrast CT=MRI scans throughout the tumour. The growth

rates were determined according to the absolute growth rate (cm3=year)

calculation [dV (latest-initial)=t]. Recurrence was defined as radiologi-

cally detected evidence of regrowth regardless of symptoms.

Results

The mean Mib-1 SI in the 184 male patients was

5.78% (SD 6.31), whereas that of the 370 female pa-

tients was 3.87% (SD 6.314). Taking the WHO classifi-

cation into consideration, this sex-related difference was

not significant (Table 1). There were no higher Mib-1

scores observed in younger patients (<37 years mean

Ki-67 LI 4.2%, SD 4.19) whereas patients with NF-II

show significantly higher mean Ki-67 LI (6.2%, SD

3.95). All NF-II cases were excluded from the following

statistical evaluations due to their different tumori-

genesis. In this series of 600 retrospectively evaluated

meningiomas no tumour was embolized pre-operatively.

After classifying 580 tumours into 6 typical cate-

gories of meningioma appearance, we found no statis-

tically significant relationship between the proliferation

index and tumour location (P¼ 0.273) (Table 2).

Table 1. Mean Ki-67 LI in meningiomas

No. of cases Ki-67 (range) Ki-67

(meanþ SD)

WHO�I 526 0–58 3.54 � 4.97

– Female 370 3.30 � 4.44

– Male 156 4.37 � 4.80

WHO�II 45 3–30 11.9 � 8.25

– Female 18 12.27 � 8.51

– Male 27 11.67 � 8.07

WHO�III 9 5–30 18.2 � 9.53

– Female 3 19.0 � 10.53

– Male 6 15.8 � 9.17

Table 2. Mean Ki-67 LI in different locations (n¼ 580)

Region Number of cases Mean Ki-67 SD

Convexity 178 5.02 5.36

CPA 144 4.78 6.75

Sphenoid wing 105 4.27 6.13

Frontobasal 67 3.57 3.84

Petroclival 54 3.84 3.15

Spinal 32 4.65 6.62

38 F. Roser et al.

WHO�I meningiomas had a 3.54% Ki-67 LI (range

0–58%, SD 4.97). Ki-67 LI in WHO�I tumours was

significantly lower than in WHO�II (atypical) and

WHO�III (anaplastic), (P<0.0001). Data are summa-

rized in Table 1.

When subdividing WHO�I meningiomas according to

the WHO histological classification we did not find a

significant Ki-67 LI difference in 379 meningothelioma-

tous (mean Ki-67 LI 3.28%), 80 fibrous (mean Ki-67 LI

3.95%), 54 transitional (mean Ki-67 LI 2.88%), 11

psammomatous (mean Ki-67 LI 1.1%), 7 angiomatous

(mean Ki-67 LI 3.0%), 7 clear cell (mean Ki-67 LI

0.7%) or 5 microcystic meningiomas (mean Ki-67 LI

4.4%) (P¼ 0.087). Patients with first time treated

meningiomas (n¼ 463) were compared with patients

with local recurrence of a previous surgically treated

meningioma (n¼ 117). First time treated meningiomas

had a mean Ki-67 LI of 3.9% vs. 6.91% in recurrent me-

ningiomas [P<0.0001]). In 25 patients with WHO�I,

6 patients with WHO�II and 3 patients WHO�III we

measured the mean Ki-67 LI from the initial tumour

operation to its second, third and in 5 cases to its fourth

local recurrence and we saw a progression of the Ki-67

LI in local recurrences in each patient (Fig. 1). There

was a transformation from benign to atypical menin-

gioma from second to third local recurrence in 16% of

the cases, whereas no dedifferentiation from WHO�I to�III or WHO�II to WHO�III was seen.

Tumour size had a mean value of 43.65 cm3 ranging

from 3–372 cm3; progesterone receptors showed a mean

index of 23.8%, ranging from 0–85%); intra-osseous

involvement was seen in 167 cases.

Male gender (increased time-to-recurrence), vas-

cularity (increased vascularity – increased time-to-

recurrence) and progesterone-receptor status (high

PR-Status – increased time-to-recurrence) have been

found to be significantly related to time-to-recurrence

(ANOVA, p<0.0005).

We then looked at correlations of these significant

variables to see which ones might be redundant in any

model to account for these parameters. Increased vascu-

larity was associated with significant increases in pro-

gesterone staining and decreases in WHO index and

Ki67 labelling. In addition, increased WHO index was

associated with decreased PR-Status and increased

Ki-67 LI. Finally, decreased progesterone staining was

associated with increased Ki-67 LI.

In 38 patients we saw a significant correlation

between the neuroradiologically assessed tumour growth

and the proliferative activity of the tumour (Fig. 2).

Analysis of the dependence of time-to-recurrence and

grade of resection was performed. Separation of all

WHO�I meningiomas with recurrences (n¼ 120) in

four different resection grades according to the Simpson

classification (S�) showed that time-to-recurrence

in completely resected meningiomas depend on the

Fig. 2. Correlation of mean Ki-67 LI and neuroradiological growth

rate in WHO�I meningiomas (n¼ 38; r¼ 0.34; p¼ 0.0001)

Fig. 1. Individual proliferation in local recurrence of meningioma

patientsFig. 3. Recurrence free survival for WHO�I and S�I resected

meningiomas

The Ki-67 proliferation antigen in meningiomas 39

resection grade (S�I 67.3 month, S�II 50.0 month, S�III

46.3 month and S�IV 40.3 month). The mean Ki-67 LI

was independent of the resection grade (S�I 5.75%, S�II

4.2%, S�III 6.76% and S�IV 7.99%).

For survival analysis WHO�II and �III meningiomas,

as well as partially resected meningiomas, were

excluded. In WHO�I and S�I resected meningiomas we

did not find any significant difference in survival accord-

ing to different mean Ki-67 LI (n¼ 169, Pearson corre-

lation R¼ 0.176, P¼ 0.36). A cut-off point of 4% was

set as the mean value of the mean Ki-67 indices in the

analysed group (Fig. 3).

Conclusion

Meningiomas are mostly benign tumours that usually

do not invade the brain parenchyma. The WHO grading

system aiming to describe different types of tumours,

frequently fails to determine the clinical behaviour of

meningiomas. Even in cases of complete removal

according to the Simpson classification the chance of

recurrence is high [48]. Pathological specimens in those

cases do not show either atypical features or histopatho-

logical signs of increased biological activity. Prolifera-

tion markers like BrdU or AgNOR have been used to

describe the clinical course in meningioma patients

[5, 27, 45]. New biochemical markers like Topo-isomer-

ase II-�, telomerase or apoptotic fragmentation [13, 29,

31, 50] reflect meningioma behaviour in conjunction

with morphological grading, but they all describe the

biological activity in atypical and anaplastic meningio-

mas better than predicting the recurrence potential in

benign meningiomas. The Mib-1 monoclonal antibody,

staining the Ki-67 antigen, can be used on paraffin

embedded specimens. Its reliability in analysing menin-

gioma growth and recurrence has been shown by several

authors [2, 33, 39, 40, 44]. The purpose of this study was

to evaluate the value of the Ki-67 antigen in predicting

the behaviour of meningiomas.

Our data suggest that there is no statistically signifi-

cant correlation between mean Ki-67 LI and recurrence

free survival in patients harbouring a benign menin-

gioma and who underwent radical tumour resection

(Fig. 3). We excluded atypical and anaplastic meningio-

mas from survival analysis because aggressive behaviour

of these meningiomas with dedifferentiation at time of

recurrence is well described through morphological stud-

ies. In terms of true recurrence, incompletely resected

meningiomas with infiltrated dura left in place or sub-

totally removed tumour tissue, which will certainly

regrow over time, would not fit into the concept of recur-

rence after radical resection and had been excluded from

the analysis as well. Even with these stringent selection

criteria a large sample could be meaningfully analysed

as we disposed of a very large number of cases from the

outset.

Møller separated different resection grades and histolo-

gy before survival analysis in 25 cases and could not

give any significant prediction with Ki-67 immunohisto-

chemistry as well [35]. Abramovich reported the

absence of a significant difference in proliferation in

59 meningioma patients who had been radically opera-

ted upon. He documented higher indices in the recurrent

group and recognized a clear overlap of the index range

between the groups [2].

These and our results differ from most of the other

studies showing a strong correlation between mean Ki-

67 LI and recurrence free survival. Ohta et al. showed a

correlation with recurrence free interval in 42 patients,

but the follow-up time was 60 month and the statistics

were performed without dividing the meningiomas

according to the WHO classification [42]. Perry et al.

showed values for interpretation of borderline atypical

meningiomas in 425 meningiomas through multivariate

analysis. Brain invasion, mitosis count>3=10 and a mean

Ki-67 LI>4.2% correlated to decreased recurrent free

survival. Based on ‘‘gross total resection’’ the statistics

summarize all grades of surgical excision, comparing a

disproportionate group of 389 patients with Ki-67

LI<4.2% versus 33 patients with Ki-67 LI>4.2%.

WHO�I meningiomas alone show an even more dispro-

portionate ratio of 325 vs. 15 patients [44]. Perry et al.

states that the Ki-67 LI influences survival, but he takes

all WHO grades together and makes no mention of Ki-67

LI influence on survival with WHO�I alone.

Our statistically more homogenous group has 169

patients with Ki-67 LI<4.2% versus 23 patients with

Ki-67 LI>4.2%, all with WHO�I and S�I resection

grade in survival analysis. Matsuno et al. and Nakasu

et al. reported a 3.2% and 3% cut-off point for higher

recurrence tendency. However 20% to 50% of the recur-

rent meningioma group were atypical, and all non-recur-

rent meningiomas were WHO�I. Survival analysis was

performed taking all patients together without dividing

for surgical resection or histological grade [32, 40]. The

small number of patients in each group and the uneven

distribution of histological grades might have addition-

ally influenced the mean LI and the survival analysis.

Failing to separate different histopathological and

resection grades expose these studies to the criticism

40 F. Roser et al.

that Ki67 may simply describe a well known phenom-

enon, in other words that more aggressive histology and

less aggressive regression correlate to shorter disease

free survival times.

The strength of our data lies furthermore in the fact,

that all meningiomas were treated surgically by one

experienced neurosurgeon (MS), morphologically diag-

nosed by one pathologist (HO) and stained by the same

method over a period of ten years. Definition of radical

tumour removal and interpretation of positive tissue

staining are therefore easier to achieve.

The proliferation index did not show any differences

concerning sex or age analysis, but in NF-II patients

showed significant higher levels. This may reflect differ-

ences in molecular biology between sporadic and NF-II

meningiomas and may be related to an earlier onset,

multiplicity or more aggressive behaviour of NF-II

tumours [4]. The proliferation index in 45 atypical and

12 anaplastic meningiomas in our series was higher than

in benign meningiomas and reflects the aggressive

histopathology described as increased vascularity and

mitosis, a loss of architectural pattern, prominent

nucleoli, nuclear polymorphism and necrosis [1, 12,

19, 25] (Table 1).

Although embolisation of meningiomas has been per-

formed for many years as a preoperative adjunct to

reduce tumour vascularity and facilitate surgical exci-

sion, it may potentially cause an erroneous diagnosis

of a high-grade lesion due to the fact that it may produce

tumour necrosis. Increase in MIB-1 labelling indices in

those tumours exhibiting necrotic foci has been demon-

strated, but it did not have any prognostic significance

[36, 41, 43].

Genetic alterations can explain biological progression.

Next to chromosome 22 anomalies, deletions of the short

arm of chromosome 1 have previously been described as

the most frequent alterations detected by cytogenetic

analysis of meningiomas [6]. Deletion of 1p and there-

fore enzyme activity loss of tissue non-specific alkaline

phosphatase (ALPL) has been proposed to be associated

with the development of atypical and anaplastic menin-

giomas [38]. The frequency of loss of heterogeneity on

chromosomes 1p, 10q and 22 increases with tumour

grade, which would support the concept that aggressive

meningiomas develop through tumour progression

[47, 51]. Attempts were also made to predict recurrence

in benign meningiomas, combining cytogenetics and

histology through a multimodal approach [24].

Some investigators reported a higher recurrence of

meningiomas at distinct locations (parasagittal, sphenoid

ridge) while others did not. [10, 19, 34]. In our study

there was no correlation between tumour location and

mean Ki-67 LI. The recurrence appears to be influenced

by accurate microsurgical removal, and this may be

location dependent.

Literature data support the view that tumour doubling

time and mean Ki-67 LI in subtotal resected meningio-

mas correlate [21, 39]. In these studies initial and recur-

rent tumour were not necessarily from the same patient,

therefore no conclusion about increased growth fraction

in the individual patient could be made [33]. We found a

strong correlation between neuroradiologically mea-

sured growth rates and mean Ki-67 LI, and for the first

time increased growth rates and mean Ki-67 LI in local

recurrencies in the individual patient. Even though we

analysed a higher number of cases for this purpose, case

numbers were still too small to statistically separate dif-

ferent stages of surgical resection [39].

The definition of tumour recurrence in a meningioma

is controversial throughout the literature. The term

‘‘radical removal’’ is a surgical definition, therefore sub-

jective so that tumour recurrence may in fact be a

regrowth. Post-operative MRI studies with contrast med-

ium can minimise this error and show the actual extent

of tumour removal.

Regrowth after surgical intervention can be silent for

a long period of time until the tumour reaches a sub-

stantial size while others will be brought to attention

sooner after compressing important structures like brain

stem, optic chiasm or sagittal sinus in parasagittal

meningiomas [46]. Besides the present study, we found

another series where recurrence is defined based on

radiological evidence of regrowth [40]. Other investiga-

tors have stated that a radiologically detected regrowth

that does not require intervention does not count as true

recurrence [13]. This is correct in terms of clinical

follow-up, but statistical analysis of morphological

features needs an accurate definition of recurrence.

The significant correlation of high vascularity and

high Ki-67 LI suggests the neo-angeogenetic capability

of meningiomas and might account for higher prolifera-

tion in these tumours as reflected by Ki-67 [7, 17]. It has

been shown that high progesterone receptor status in be-

nign meningiomas is associated with lower recurrence

rate and vice versa [9, 14]. Our data support this negative

correlation of high proliferation index in meningiomas and

low progesterone receptor level showing ‘‘protection’’

against recurrence.

In our series we observed elevated proliferative activ-

ity in recurrent meningiomas throughout the histological

The Ki-67 proliferation antigen in meningiomas 41

grouping, like most other studies had shown [1, 2, 32, 33,

35, 40, 42]. A decrease of the LI has only been reported

by Madsen et al. [30] (Table 3). Caution is recommended

when using the proliferation index as the sole prognostic

indicator or as a substitute for morphological diagnosis

due to the overlap in each group (WHO�I mean Ki-67 LI

0–30%, WHO�II mean Ki-67 LI 3–35% or WHO�III

mean Ki-67 LI 5–58%) [1, 22, 26, 28]. This might

be due to the heterogeneity of biological activity

within the tumour tissue [2, 46]. Proliferating cells in

all histological grades were found to be distributed het-

erogeneously throughout the tumour, especially in recur-

rences [42]. It is debatable that the focal accumulation

of proliferation may affect tumour recurrence for the

‘‘highest area’’ counting method [40]. We used the

‘‘highest area’’ counting method to minimize missing of

focal accumulation of biological activity within the me-

ningioma tissue, as it is recommended by Nakasu et al.

[40]. This is an important issue when considering modern

neurosurgical techniques, where only small parts of tu-

mour with unknown precise location of the tissue reaches

the pathologist. Indeed it is debatable whether recognized

areas of high mitotic activity in meningiomas determined

with either counting method, reflect the proliferation

status of the whole tumour.

Studies assessed the expression of leucocyte integrins

and macrophage-associated antigens in meningiomas to

detect any influence on proliferation capability. Evi-

dence of a correlation between the Ki-67 proliferation

index and macrophage infiltration could not be provided,

although it has been suggested that the expression of

leucocyte antigens could play a role in the attraction

of immunocompetent cells in the stroma of meningio-

mas. As proliferation cells in meningiomas are spread

heterogeneously within the tumour and macrophage=

lymphocyte infiltration has been reported to be mainly

at the tumour margins, only double labelling methods

could give insight into this phenomenon and exclude

errors in statistical evaluation [37].

In our series more than 80 patients have a mean Ki-67

LI of 1% with recurrence times ranging from 11 to 148

month. Therefore a cut-off value over which a tumour

becomes suspicious cannot be given. Precise values from

different laboratories are not applicable to other institu-

tions because of differences in methodology, counting

procedures and interpretation of the results as reflected

by the relatively wide range of initial and recurrent

Ki-67 LI determined by several investigators (Table 3).

Despite our single center study individual set cut-off

points even for our Neurosurgical Department would

be questionable due to the heterogeneity of meningio-

mas in the different groups (resection grade, histology,

Ki-67).

In histopathological borderline cases, with some but

not convincing aspects of atypia, the Ki-67 LI, combined

with the routine histopathological workup can provide

more insight in to the behaviour of a meningioma, par-

ticularly in the presence of high vascularity, low PR-

status, subtotal resection and recurrence [44]. High

scores are worrisome and should lead to a more close

follow up for evidence of recurrent tumour, but the con-

fidence in high LI should not interfere with the decisions

for treatment plans as some authors recommend [32, 40,

49]. Further studies are needed to establish new indica-

tors that can describe meningioma behaviour in a reli-

able and predictive way.

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Table 3. Meningioma recurrence determined by mean Ki-67 LI. Review of the literature

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patients

F=U time

(month)

Mean Ki-67 LI (%)

initial

Mean Ki-67 LI (%)

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Nakaguchi et al., Cancer 1999 22 64 1.8 3.0

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Comment

This work on a large series of patients confirms the value of the Ki-67

labelling index for the classification of meningiomas. However, it can

not serve as a predictive factor on its own.

N. de Tribolet

Correspondence: Florian Roser M.D., Department of Neurosurgery,

Klinikum Hannover Nordstadt, Haltenhoffstr. 41, 30167 Hannover,

Germany. e-mail: f.roser@gmx.de

44 F. Roser et al.: The Ki-67 proliferation antigen in meningiomas