Neurosurg Rev (2004) 27: 238–245
DOI 10.1007/s10143-004-0340-y
ORIGINA L ARTI CLE
Stefan Wolfsberger . Soroush Doostkam .
Hans-Gerd Boecher-Schwarz . Karl Roessler .
Michael van Trotsenburg . Johannes A. Hainfellner .
Engelbert Knosp
Progesterone-receptor index in meningiomas: correlation with
clinico-pathological parameters and review of the literature
Received: 23 February 2004 / Revised: 31 March 2004 / Accepted: 31 March 2004 / Published online: 27 May 2004
# Springer-Verlag 2004
Abstract For recurrent and untreatable meningiomas
alternative therapies, such as anti-progesterone treatment,
have been sought. However, the few clinical studies have
not determined progesterone receptor (PgR) expression in
most cases, and studies correlating quantitative PgR
expression (PgR index) with clinico-pathological variables
are scarce. The aim of our study was to assess the PgR
indices in a consecutive series of meningiomas and
correlate these values with clinico-pathological para-
meters. We analyzed immunohistochemically 82 consecu-
tive meningioma specimens (73 primary and nine recur-
rent tumors) for PgR and Ki-67 antigen (MIB-1). The
male/female ratio was 1:1.7, and median age at the time of
surgery was 57 years (range 29–77 years). The series
comprised 55 grade I (subtyped as 36 meningothelial,
seven fibrous, nine transitional, two psammomatous, and
one angiomatous), 23 grade II, and one grade III
S. Wolfsberger (*) . K. Roessler . E. Knosp
Department of Neurosurgery, General Hospital (AKH), Medical
University Vienna,
Waehringer Guertel 18–20,
1097 Vienna, Austria
e-mail: stefan.wolfsberger@akh-wien.ac.at
Tel.: +43-1-404004565
Fax: +43-1-404004566
S. Wolfsberger . J. A. Hainfellner
Institute of Neurology, General Hospital (AKH), Medical
University Vienna,
Vienna, Austria
S. Doostkam
Department of Neuropathology, Johannes Gutenberg
University,
Mainz, Germany
H.-G. Boecher-Schwarz
Department of Neurosurgery, Johannes Gutenberg University,
Mainz, Germany
M. van Trotsenburg
Division of Gynaecological Endocrinology and Assisted
Reproduction, Department of Obstetrics and Gynaecology,
Medical University Vienna,
Vienna, Austria
meningiomas. Nuclear immunostaining for PgR was
positive in 56 meningioma specimens (71%). PgR index
was 21.4±2.8% (mean ± SE; range 0–79%). Significantly
higher expression was found in male patients in the age
group <50 years than in those ≥60 years and in grade I
meningothelial meningiomas than in fibrous and transi-
tional subtypes. There was a trend to lower PgR indices in
non-benign meningiomas. Cell proliferation rate (MIB-1
index) was 4.4±0.4% (mean ± SE; range 0.3–15.4%).
Significantly higher MIB-1 indices were found in male
than female patients,in recurrent than primary and in grade
II than grade I meningiomas. We observed a trend to
higher PgR indices in meningiomas with MIB-1 index
<5%. In sum, the highest PgR index in our series was
observed in patients under the age of 50 years with WHO
grade I meningiomas of the meningothelial subtype and
low cell proliferation indices. If hormonal therapy has a
direct action on the PgR, these patients should respond
best to anti-progesterone treatment. We conclude that PgR
index is variable in meningioma, depending on clinical
parameters and histopathological features. Stratification of
anti-progesterone therapy trials on the basis of PgR index
should be considered.
Keywords Meningioma . Progesterone receptor .
Proliferation marker . MIB-1 . Clinico-pathological study
Introduction
Accounting for 13–26% of all primary intracranial
neoplasms [41], meningiomas are among the most
frequent tumors that affect the central nervous system.
Although >90% are slowly growing and histologically
benign (WHO grade I), up to 20% have been reported to
recur within 10 years [5]. For the 6% atypical (WHO grade
II) and the 2% malignant (WHO grade III) meningiomas,
recurrence rates are 50% and 66% at 10 years, respectively
[42].
Surgical resection is the treatment of choice. The goal is
total removal of tumor, adjacent dura and bone (Simpson
 239

grade I), as complete resection is the most important
prognostic factor for recurrence besides WHO grade and
tumor cell proliferation rate [41]. After 10 years recurrence
rates are around 9%, even if a Simpson grade I resection
has been performed. If only tumor debulking has been
performed (Simpson grade V), recurrence rates are 40%
[5, 44, 62]. In the case of incomplete resection, radio-
surgery and/or fractionated radiotherapy can be applied
and may reduce recurrence to rates comparable to total
tumor resection [47]. However, for the few patients with
meningiomas that (1) tend to recur despite all therapeutic
efforts or (2) are too large and/or unfavorably located for
successful treatment without considerable morbidity,
alternative medical treatments have been sought.
The assumption that sex hormones may play a funda-
mental role in the development, growth and regression of
meningiomas is based on the following observations. (1)
The incidence of meningiomas is higher in females than in
males (ratio 3:2–2:1) [41]. (2) Enlargement of meningio-
mas and aggravation of symptoms has been reported in
association with high serum progesterone levels, e.g.,
during the luteal phase of the menstrual cycle or during
pregnancy, and symptoms subsided when elevated pro-
gesterone levels returned to normal [2, 51]. (3) There is a
non-random coincidence with breast cancer [40].
Following the first report on the presence of estrogen
receptors (ER) in meningioma tissue by Donnel et al. [17]
numerous papers have dealt with steroid receptor expres-
sion in this tumor entity [1, 3, 4, 6, 8, 10–15, 18, 19, 21,
24, 26–28, 30, 32, 34–38, 43, 45, 50, 52, 55–58, 60, 63–
66]. Although ER expression is very low or undetectable
by immunocytochemical assay (ICA) (Table 1), the
presence of progesterone receptors (PgR) has been
reported by many studies in as many as two-thirds of
meningiomas [8–11, 12, 14, 18, 24, 26, 28, 30, 34, 36–38,
52, 55, 56, 60]. Its precise function in terms of influencing

Table 1 Progesterone receptor Patient subgroup n PgR index MIB-1 index

indices and cell proliferation
indices in meningiomas
a
Mean ± SE (%) P b
Mean ± SE (%) Pb

Overall tissue specimens 82 21.4±2.8 4.4±0.4

Primary meningioma 73 20.9±3.0 NSa 4.0±0.4 0.029
Recurrent meningioma 9 24.9±7.7 7.3±1.4
Gender
Male 30 24.7±4.7 NS 6.1±0.8 0.021
Female 52 19.3±4.7 3.4±0.4
Age
Median (range) 57 years (29–77)
Male <50 years 6 41.4±10.4 0.050 5.0±1.8 NS
50–59 years 11 24.6±9.1 6.5±1.5
≥60 years 13 17.2±5.4 6.2±1.2
Female <50 years 16 25.0±6.2 NS 2.8±0.7 NS
50–59 years 16 19.0±6.6 3.5±0.5
≥60 years 20 14.9±5.0 3.8±0.8
Location
Convexity 40 23.4±4.3 NS 3.9±0.5 NS
Cranial base 40 20.5±3.7 5.0±0.6
Spinal 2 0.7±0.7 – 1.2±0.9 –
WHO grade
I 55 22.9±3.7 NS 3.5±0.4 0.001
II 23 15.8±4.0 6.6±0.9
III 1 0.0 – 9.3 –
NDa 3
Grade I subtypes
Meningothelial 36 27.5±4.8 0.032 3.7±0.6 NS
Fibrous 7 13.5±7.6 2.1±0.5
Transitional (mixed) 9 12.6±7.7 4.1±0.6
Psammomatous 2 6.0±0.1 ND 0.5±0.1 ND
Angiomatous 1 50.1 – 4.5 –
Male
Meningothelial 10 29.3±10.3 ND 3.6±1.3 ND
a
SE, standard error; ND, not Fibrous/transitional 3 7.6c±7.7 4.2b±1.7
defined; NS, not significant Female
b
Mann–Whitney U-test, Krus- Meningothelial 26 26.7±5.5 0.002 3.8±0.7 NS
kal–Wallis test Fibrous/transitional 13 5.1±3.6 2.9±0.5
c
Median value given
240
tumor growth, however, is still a matter of research [15,
14, 65, 66].
In vitro studies recorded meningioma shrinkage under
anti-progesterone treatment [7, 48, 53, 54]. In the clinical
setting, however, this effect could not be reproduced
unequivocally [16, 22, 23, 25, 39, 61]. This may be due to
(1) small study cohorts for hormonal therapy, as cases that
have exhausted surgical and radiotherapeutic treatment
options are rare; (2) the follow-up for the detection of
changes in size needs to be rather long in this mostly
benign tumor; and (3) PgR expression in these unresect-
able meningiomas has not been assessed in most cases.
Due to the therapeutic implications it is of interest to
know PgR expression in meningiomas in quantitative
terms. Early studies quantified PgR concentration using in
vitro methods (for a review see Black [5]). These laborious
techniques are not applicable in the routine diagnostic
setting. However, routine immunohistochemical detection
of PgR expression has become feasible. Nuclear binding
signals of anti-progesterone immunocytochemistry allows
quantification of PgR expression (PgR index). So far,
studies determining and correlating exact PgR index with
clinico-pathological variables are scarce [9] or semiquan-
titative [11, 24, 30, 34, 50]. In the present study we
assessed the PgR indices in a consecutive series of
meningiomas and correlated these values with clinico-
pathological parameters.
Patients and methods
Patients
For the present study, clinical data and meningioma tissue speci-
mens were collected from 82 consecutive surgeries performed
during a 28-month period. The cohort comprises 73 primary and 9
recurrent meningiomas of 78 patients. The male/female ratio was
1:1.7; median age at the time of surgery was 57 years (range 29–77
years). Age-groups were defined as <50, 50–59 and ≥60 years in
order to form statistically comparable subgroups. Thereby, the first
group corresponds to pre-menopausal, the last group to post-
menopausal age in women. Tumor location was rated as convexity
(n=40), cranial base (n=40) and spinal (n=2). Tumor typing was
performed according to standard criteria of the World Health
Organization (WHO) [41]: WHO grade I meningiomas were
histologically subtyped as meningothelial (n=36), fibrous (n=7),
transitional (n=9), psammomatous (n=2), and angiomatous (n=1).
Meningiomas were defined as WHO grade II if there was increased
mitotic activity or three or more of the following features: loss of
cellular architecture, increased cellularity, nuclear pleomorphism,
focal necrosis, and brain parenchymal invasion. From these criteria,
the series includes 55 grade I, 23 grade II, and 1 grade III
meningiomas; no data were available in three patients.
Methods
Immediately after surgical removal, tissue specimens were stored in
liquid nitrogen at −80°C. Immunohistochemistry was performed on
serial cryostat section cut at a thickness of 4 μm. For detection of
PgR the Abbott PgR-ICA kit (Abbott, Germany) with rat monoclo-
nal antibody (KD68, prediluted) [58] was used. For detection of Ki-
67 the primary antibody MIB-1 (dilution 1:20; Dianova, Germany)
was used. Visualization of antibody binding was performed by
peroxidase–antiperoxidase complex in case of PgR and by strepta-
vidin–biotin–peroxidase complex in case of Ki-67. Diaminobenzi-
dine was used as chromogen and Harris hematoxylin for counter-
staining. Negative controls included omission or substitution of the
primary antibodies by nonspecific, isotype-matched rat antibodies
on parallel sections. MIB-1 and PgR immunolabeling were assessed
as nuclear staining on subsequent sections using the VIDAS image
analyzer (Kontron Elektronik, Munich, Germany) connected to a
light microscope unit (Zeiss, Oberkochen, Germany). In each
specimen, a total of 2,000 tumor cell nuclei were evaluated in “hot
spots,” i.e., fields showing the highest density of PgR- and MIB-1-
immunopositive cells. The fraction of immunolabeled tumor cell
nuclei was expressed as the mean percentage (=index) of ten
evaluated fields of one tissue specimen.
For statistical analyses SPSS version 10.0.7 software (SPSS, Inc.,
Chicago, USA) was used. Values are presented as mean ± standard
error. MIB-1 cell proliferation index and PgR index were compared
with each other and in clinical–pathological subgroups. Due to a
non-normal distribution of data non-parametric tests (Mann–Whit-
ney U and Kruskal–Wallis for comparison of two or more factors,
respectively) were used. A two-tailed P value of <0.05 was
considered significant.
Results (Table 1, Figs. 1, 2)
Progesterone receptor (PgR)
Nuclear immunostaining for PgR was positive in 56 (71%)
and negative in 23 (29%) of 79 tissue specimens. In three
specimens, PgR immunoassay was not possible. PgR
positivity was not related to gender or WHO grades I or II.
The single case of WHO grade III meningioma was PgR
negative. The overall mean percentage of PgR-immuno-
stained nuclei (PgR index) was 21.4±2.8% (range 0–79%).
No statistically significant difference of PgR index was
observed in subgroups of primary vs recurrent meningi-
oma, male vs female gender, convexity vs skull base
location and WHO grade I vs II. There was a trend to
higher PgR indices with younger age (R=−0.2; non
significant). Significantly higher PgR indices, however,
were observed in male patients in the age-group <50 years
than ≥60 years (41.4±10.4 vs 17.2±5.4%; P=0.036).
Among histo-morphologic subtypes of WHO grade I
meningiomas, meningothelial tumors had significantly
higher PgR indices than the group of fibrous and
transitional (mixed) meningiomas (27.5±4.8 vs 13.0
±5.2%; P=0.032). This difference was even greater in
the subgroup of females (P=0.002). In males, however, no
statistically valid comparison with the meningothelial
subtype was possible due to small sample size of fibrous
and transitional tumors (n=3).
Cell proliferation marker MIB-1
Immunostaining with MIB-1 antibody yielded interpreta-
ble results in all 82 tumor specimens. Overall mean MIB-1
index was 4.4±0.4% (range 0.3–15.4%). Higher MIB-1
indices were found in male than in female patients (6.1
±0.8 vs 3.4±0.4%; P=0.021). No differences in cell
proliferation rate were observed in age-groups and
convexity vs skull base location. MIB-1 index increased

Fig. 1 Male patient, age 45, meningioma of the petrous apex: WHO
grade I, meningothelial subtype; a MIB-1 1.2%, b PgR index 67.3%
with WHO tumor grade: grade I tumors had significantly
lower MIB-1 counts than grade II meningiomas (3.5±0.4
vs 6.6±0.9%; P=0.001; Figs. 1, 2). In line with these
results, the single case of grade III meningioma had an
even higher MIB-1 labeling index of 9.3%. Among histo-
morphologic subtypes of WHO grade I tumors, no
differences of MIB-1 indices were observed. There was
a trend to higher PgR indices in meningiomas with MIB-1
index <5% (Figs. 1, 2). However, this inverse relation did
not quite reach statistical significance (P=0.061). Recur-
rent meningiomas had significantly higher MIB-1 indices
than primary tumors (7.3±1.4 vs 4.0±0.4%; P=0.029),
apparently due to the higher incidence of WHO grade II or
III tumors in the recurrent vs primary group (89 vs 22%,
respectively).
Discussion
The few meningioma patients with either recurrent,
progressive and symptomatic tumors after repeated sur-
gery and radiotherapy and the large meningiomas that are
primarily unresectable without major morbidity pose a
241
Fig. 2 Female patient, age 58, meningioma at the superior sagittal
sinus: WHO grade II; a MIB-1 6.3%, b no PgR expression
major therapeutic challenge [47]. To define the subgroup
of patients which could be successfully treated with anti-
progesterone therapy, we quantitatively assessed the PgR
index in a consecutive cohort of patients with meningioma
and correlated these data with clinico-pathological vari-
ables.
In 1988 Press and Greene [58] first reported a
monoclonal antibody targeted against the PgR localized
in the cell nucleus. From then on, most studies used
immunocytochemical assays for the detection of PgR
expression (Table 2). So far, a strong expression of PgR in
meningiomas has been reported by most authors: A review
of the literature on clinico-pathologic studies since 1988
revealed a mean of 69% of meningiomas positive for PgR
(range 10–100%) [4, 8–11, 12, 14, 18, 24, 26, 28, 30, 34,
36, 38, 52, 55–57, 60]. This corresponds well to our
present series with PgR immunopositivity in 71% of all
meningiomas. In our data, the overall mean PgR immu-
nolabeled cell index was 21.4±0.4%. Bouillot et al. [9]
was the only other study in the literature that correlated not
only PgR positivity status but also quantitative PgR
indices to clinico-pathological variables. However, a
Table 2 Studies on PgR expression in meningiomas with clinico-pathological correlations (for prior studies refer to Black 1993 [5]). PgR, progesterone receptor; ER, estrogen receptor; Ki-
242

67, cell proliferation related antigen; S, significant; NS, not significant

Author Year n Assaya PgR (%) ER (%) Ki-67 (%) Correlation with PgR expression Other factors studiedb
Gender Age Grade Subtypec Ki-67

Present study 2004 82 ICA 71 ND 4.4 No Yesd Yes (NS) m>t+f (S) Yes (NS) –
Gursan [24] 2002 110 ICA 72 ND 0.98 f>m (S) No ND m>t>f Yes –
Verheijen [66]/Blankenstein [8] 2002/2000 386 LBA 77 13 ND f>m (S) – – – – Bcl-2, Bax
Fewings [18] 2000 60 IFT 48 ND ND No ND Benign only No – –
Perry [56] 2000 175 ICA 33 ND ND No ND Yes (S) No – Merlin, DAL-1
Carroll [14] 1999 33 ICA/PCR 64 26/38 ND No No ND ND – ER-α, ER-β
Hilbig [28] 1998 116 ICA 53 0 ND No No No No – –
Hsu [30] 1997 70 ICA 83 9 ND f>m (S) No Yes (S) No – –
Bozzetti [10] 1995 46 ICA 70 0 ND No No ND ND – –
Nagashima [52] 1995 39 ICA 72 0 0–16 f>m (S) ND Yes (S) ND Yes –
Bouillot [9] 1994 52 ICA 53 0 –e No No Yes (S) m+t>f (S) ND pS2
Kuratsu [38] 1994 22 DCC 89 0 ND No ND No No – PDGF, PDGF-R, EGF-R
Khalid [34] 1994 34 ICA 100 0 ND No No ND ND – ER-D5
Carroll [12] 1993 33/11 NBA/ICA 64 ND ND f>m (S) ND No No – –
Brandis [11] 1993 61 ICA 61 0 ND No ND Yes (Sf) ND – –
Maxwell [50] 1993 9 NBA/ICA 88 0 ND ND ND ND No – Androgen-receptor
Perrot-Applanat [55] 1992 36 ICA 72 0 3 f>m (NS) No Yesg (S) m+t>f (S) No –
Schrell [60] 1990 50 ICA 10 0 ND – – – – – –
Kostron [37] 1990 58 DCC 69 20 ND f>m (NS) ND Yes (S) ND – –
Halper [26] 1989 52 ICA 89 0 ND No No No ND – –
a
ICA, immunocytochemical assy; LBA, ligand binding assay; PCR, polymerase chain reaction; IFT, isoelectric focusing technique; NBA, Northern blot analysis; DCC, dextran-coated
charcoal technique
b
Bax, Bcl-2 associated X protein; DAL-1, differentially expressed in adenocarcinoma of the lung; PDGF(-R), platelet derived growth factor (receptor); EGF-R, epidermal growth factor
receptor; ER-D5, estrogen receptor-related antigen
c
Histologic subtypes: m, meningothelial; t, transitional (mixed); f, fibrous
d
Significantly higher PgR indices in males >50 years as compared to males >60 years
e
Ki-67 > 1% in 21% of cases
f
Significant only for male subpopulation
g
Grading by non-standard score

subgroup of patients with highest PgR indices was not
defined.
Gender
Although some studies reported significantly more PgR-
positive meningiomas in females than males [8, 24, 30,
52], others, including our own data, could not confirm
these findings [9, 10, 14, 18, 26, 34, 37, 38].
WHO grade
PgR positivity has been reported to inversely correlate
with tumor grade by many authors [9, 11, 28, 30, 37, 52,
55, 56]. In line with their findings, we observed a
reduction of PgR index from WHO grade I to grade II and
a PgR-negative WHO grade III tumor (Table 1). Therefore
meningiomas appear to lose PgR expression in the course
of tumor progression thus reducing the biological target of
anti-hormonal therapy. This may limit the clinical
usefulness of anti-PgR therapy approaches, as WHO
grade II and III meningiomas and meningiomas with high
proliferation index are particularly prone to recurrence.
Histologic subtypes
Several studies reported significant differences in PgR
positivity among meningothelial, transitional, and fibrous
meningiomas [9, 24, 55]. PgRs are also present in normal
arachnoid cells [34], which constitute the main tumor cell
type of meningiomas [41]. As the well-differentiated
meningothelial subtype shares many histological features
with normal arachnoid cells [33], it is not surprising, that
the PgR expression is higher in this meningioma subtype.
Our present series is in favor of this explanation as PgR
indices were significantly higher in the meningothelial
than in the transitional and fibrous subtypes (Table 1).
Cell proliferation rate (MIB-1 index)
High cell proliferation rate has been reported to negatively
correlate with outcome [31] and to strongly predict
recurrence of meningiomas [29]. In line with these results,
we observed significantly higher MIB-1 proliferation
indices in the nine recurrent meningiomas than in the
primary tumors (Table 1), indicating the more aggressive
biological behavior of the recurrent subgroup. The mitotic
activity is a strong contributor to the tumor grading system
as defined by the WHO [41]. The MIB-1 antibody is
targeted against the Ki-67 antigen, which is expressed in
proliferating cells throughout the cell cycle [20] and
should therefore positively correlate with mitotic activity.
We observed significantly higher MIB-1 cell proliferation
indices in grade II than in grade I tumors in our data
(Table 1) and MIB-1 positively correlated with tumor
243
grading (Spearman’s R=0.4; P<0.001). This is in line with
the results of Hsu et al. [31]. In our cohort, MIB-1 cell
proliferation rates were significantly higher in males than
in females (Table 1), confirming observations made by
other authors [31, 49, 59]. A possible explanation for this
finding is that male patients more commonly present with
non-benign meningiomas than females: in this consecutive
study, 50% of male patients had atypical (grade II)
meningiomas and thus significantly more non-benign
tumors than females (P=0.003). Nagashima et al. [52]
found significantly lower cell proliferation rates in
meningiomas with positive PgR immunostaining than in
tumors negative for PgR. In line with their findings, MIB-
1 index in our series was higher in meningiomas with
weak or no PgR expression than in those with strong PgR
expression (cutoff 5%). However, this inverse correlation
did not reach significance (P=0.061).
Recurrence
As progesterone is thought to play a major role in the
development and growth of meningiomas, follow-up
studies have evaluated PgR expression as a prognostic
factor for outcome prediction [11, 18, 30, 63]. Brandis et
al. [11] reported that the presence of PgR is a favorable
prognostic factor in patients with meningiomas. According
to the multivariate analysis of Hsu et al. [30] PgR
negativity is a highly significant predictor for shorter
progression-free survival and thus for worse outcome.
Fewings et al. [18] confirmed these results by the
observation that benign PgR-positive meningiomas are
significantly less likely to recur. Recently, Strik et al. [63]
found significantly higher risk for recurrence in the case of
low expression of PgR, but not in the case of high
proliferation rate. However, the latter finding may be due
to the fact that only benign, WHO grade I tumors were
included in the study. A limitation of our study is the small
group of recurrent meningiomas (n=9) which did not allow
us to draw statistically significant comparisons. However,
as we prospectively studied a consecutive patient cohort,
the number of recurrent meningiomas operated during this
time was random.
To gain insight into the action of progesterone on
meningioma growth, various in vitro studies using
progesterone agonists or antagonists have been carried
out [7, 32, 43, 46, 48, 53, 54]. Although these studies
showed promising effects of anti-progesterone therapy on
meningioma growth, clinical therapy trials have so far
remained scarce: In 1990, Haak et al. [25] reported two
cases of recurrent inoperable meningiomas successfully
treated with mifepristone for 8 and 12 months, respec-
tively. Relief of visual symptoms occurred in both,
decrease of tumor size in one patient. In 1991, Grunberg
et al. [23] reported on 14 patients with unresectable
meningioma who received mifepristone treatment for 2–31
months. Tumor regression was observed in five patients<;
an additional three patients experienced subjective im-
provement of ocular muscle function or relief from
244
headache. Tumor progression was found in three patients,
two of them harboring malignant meningiomas. In a series
of ten patients with inoperable recurrent meningioma,
Lamberts et al. [39] in 1992 observed tumor control in six,
regression in three and improvement of headaches in five
of ten meningioma patients by mifepristone treatment.
Davis et al. [16] treated 11 patients, four with recurrent
meningiomas, with gestrinone, a synthetic antiprogester-
one. After a follow-up of 38 months, there was no clinical
or radiological change. A case report of a 21-year-old
woman with a recurrent left parietal meningioma was
presented by Sharif et al. [61] in 1998: The patient
presented 18 months after initial subtotal surgery, and 3
weeks after abortion. Gestrinone therapy was initiated for
2 months, leading to a dramatic tumor shrinkage to less
than 20% of the previous volume, and the patient became
asymptomatic. In 2001, Grunberg et al. [22] published an
abstract on a phase III double-blind placebo-controlled
study of mifepristone for the treatment of unresectable
meningioma, which failed to show any difference of the
antiprogesterone therapy as compared to placebo. How-
ever, no data on PgR expression are provided.
Summary and conclusion
The few clinical studies on anti-progesterone treatment in
patients with meningiomas have reported contradictory
results because (1) patient selection is difficult, as
unresectable recurrent and irradiated meningiomas are
rare; (2) small changes in tumor size require long follow-
up; and (3) PgR index has not been determined in most
cases. According to our data the highest PgR index is
observed in patients under the age of 50 years with WHO
grade I meningiomas of the meningothelial subtype and
low cell proliferation index. If hormonal therapy has a
direct action on PgR, these patients should respond best to
anti-progesterone treatment. Altogether we conclude that
PgR index is variable in meningioma, depending on
clinical parameters and histopathological features. Strati-
fication of anti-progesterone therapy trials on the basis of
PgR index should be considered.
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