Original Article
Progesterone Receptor Is Responsible for Benign Biology of Skull Base Meningioma
Yasuhiro Kuroi1, Kasumi Matsumoto2, Makoto Shibuya3, Hidetoshi Kasuya1
- OBJECTIVE: Many studies have been performed to eval-
uate the roles of estrogen receptor and progesterone
receptor (PGR) in meningiomas, but their influence on
tumor behavior remains unclear.
- METHODS: We retrospectively analyzed patients with
meningioma who underwent surgical resection at our
institute. Patients with data for immunohistochemical
staining of estrogen receptor, PGR, and Ki-67 were
included.
- RESULTS: The study included 161 patients comprising 61
skull base and 100 noneskull base meningiomas. Histolog-
ically, the number of patients with World Health Organiza-
tion (WHO) grade I, II, and III disease were 132 (82.0%), 22
(14.7%), and 7 (4.4%), respectively. Tumor recurrence was
observed in 21 (13.0%). Negative PGR, high Ki-67 index,
incomplete resection, and WHO grade II or III were signifi-
cantly correlated with tumor recurrence and shorter
recurrence-free survival. Skull base meningiomas were
difficult to remove entirely; 31 patients (50.8%) with skull
base and 77 patients (77.0%) with noneskull base menin-
giomas had overall complete removal (P [ 0.0006). Ki-67
indices, proportion of WHO grade II or III, and recurrence
rate or recurrence-free survival did not differ between the
tumor locations. The only difference was the proportion of
patients with positive PGR, which was significantly higher
for skull base meningiomas (61.5
33.4% vs. 42.2
35.7%,
P [ 0.0009).
- CONCLUSIONS: Although skull base meningiomas are
often incompletely resected, there were no differences in
Key words
- Estrogen receptor
- Progesterone receptor
- Skull base meningioma
- Tumor malignancy
Abbreviations and Acronyms
ER: Estrogen receptor
GTR: Gross total resection
KPS: Karnofsky performance status
PGR: Progesterone receptor
RFS: Recurrence-free survival
STR: Subtotal resection
WHO: World Health Organization
WORLD NEUROSURGERY -: e1-e7, - 2018
recurrence-free survival or recurrence rate between skull
base and noneskull base meningiomas. As the Ki-67 index
and WHO grade were not different between these loca-
tions, the high rate of positive PGR may be responsible for
the benign biology of skull base meningiomas.
INTRODUCTION
M
eningiomas are the most common primary central
nervous system neoplasms originating from arachnoid
cap cells, and constitute 23.8% of all primary brain
tumors in Japan.1 Although most meningiomas are slow growing
and histologically benign,2 some of them recur and exhibit
malignant transformation; therefore, prediction of recurrence is
a major clinical concern when treating meningiomas. To date,
the World Health Organization (WHO) classification of
meningioma is most widely used for predicting prognosis.
Although it is purely histopathological, it is currently the most
powerful predictor.
The expression of estrogen receptor (ER) and progesterone
receptor (PGR) has long been examined as alternative prognostic
markers because meningiomas differ between the sexes. The
female:male ratio is approximately 2:1,1 and atypical and anaplastic
meningiomas have a male predominance.3 Furthermore, there are
reports on the rapid growth of meningioma during pregnancy4
and in postmenopausal patients who received exogenous
hormone replacement therapy,5 suggesting that sex steroids play
an important role in the growth of meningiomas. Recently, their
significance has been investigated. PGR expression was found in
39%e88% of meningiomas, but ER levels were undetectable.3,6-12
From the 1Department of Neurosurgery, Tokyo Women’s Medical University Medical Center
East, Tokyo; 2School of Medicine, Tokyo Women’s Medical University, Tokyo; and 3Central
Laboratory, Hachioji Medical Center, Tokyo Medical University, Tokyo, Japan
To whom correspondence should be addressed: Yasuhiro Kuroi, M.D.
[E-mail: kuroi.yasuhiro@twmu.ac.jp]
Citation: World Neurosurg. (2018).
https://doi.org/10.1016/j.wneu.2018.07.100
Journal homepage: www.WORLDNEUROSURGERY.org
Available online: www.sciencedirect.com
1878-8750/$ - see front matter ª 2018 Elsevier Inc. All rights reserved.
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 ORIGINAL ARTICLE
YASUHIRO KUROI ET AL. ROLE OF PROGESTERONE RECEPTOR IN MENINGIOMAS

Moreover, some researchers argue that negative PGR expression is
correlated with high proliferative indices, high tumor grades, high
cellular proliferative indices, and tumor recurrence.3,11
Skull base meningiomas are considered to be genetically
different from their non-skull base counterparts.13,14 Although
many studies have demonstrated that skull base meningiomas
have lower proliferative indices, these data and their association
with recurrence are inconsistent.15,16
The aim of this study was to retrospectively review patients with
meningioma we treated during the past 10 years focusing on ER
and PGR expression in association with clinical behavior.
Tumor Recurrence and Follow-Up Period
Any tumor growth resulting in symptomatic changes requiring
reoperation or radiation was considered significant recurrence.
Planned postoperative adjuvant radiation was excluded from
recurrence. In asymptomatic patients, tumor recurrence was
defined as 10% or 2 mm growth in the greatest diameter. To
review the relationship between tumor prognosis and expression
of ER and PGR, we set the start point of follow-up on the day that
ER and PGR data were obtained for the tumor specimen. Patients
with a past history of surgery or radiotherapy for meningioma
were defined as having nonede novo meningioma and those
without were defined as having de novo meningioma.

METHODS

Patient Population Statistical Analysis

We retrospectively analyzed patients at the Tokyo Women’s Analyses were conducted using JMP software, version 13.0 (SAS
Medical University Medical Center East, Tokyo, Japan, treated Institute Inc., Cary, North Carolina, USA). Student’s t-test and chi-
between April 1, 2007, and November 15, 2016, with histologically square test were used for comparison of the 2 groups. Kaplan-
confirmed intracranial meningiomas. We selected patients who Meier analysis was used to assess the recurrence-free survival
underwent all 4 histopathological examinations, including (RFS). The Wilcoxon test was used to assess significance for RFS.
hematoxylin-eosin staining, Ki-67 (MIB-1) staining, and ER and A P value of <0.05 was considered significant. This study was
PGR immunostaining. Patients with insufficient follow-up (less performed after approval by the institutional review board at
than 1 year without recurrence), those with genetically diagnosed Tokyo Women’s Medical University.
neurofibromatosis type 2, or those who underwent reoperation
more than 3 times were excluded from the study.
Table 1. Characteristics of 161 Meningiomas with or without
The extent of microsurgical resection was documented using
Recurrence
the Simpson grade (gross-total resection [GTR], Simpson grades I
and II; and subtotal resection [STR], Simpson grades IIIeIV) Recurrence No Recurrence
based on surgical records. Patients with a history of gynecological (n [ 21) (n [ 140) P Value
disease, such as uterine myoma, ovarian tumor, and breast or
uterine cancer, which may have affected progesterone or ER Sex (female) 15 109 0.5138
expression, were regarded as having gynecological disease. Age (years) 61.4
15.1 60.6
13.4 0.8123
Ki-67 (%) 9.3
8.9 3.9
4.6 <0.0001
Histopathology and Immunohistochemical Analysis Ki-67  4.2% 12 40 0.009
Hematoxylin-eosin staining was performed for histological diag- Denovo tumor 6 127 <0.0001
nosis. Histological subtypes and grades were classified according to
Multiple 5 10 0.0143
the 2007 WHO classification criteria. Immunohistochemical stain-
ing was carried out for ER, PGR (Ventana Medical Systems Inc., Location (skull base) 9 52 0.6147
Tucson, Arizona, USA), and Ki-67 (DAKO, Glostrup, Denmark) Gynecological diseases 3 33 0.3409
according to the manufacturer’s instructions for primary antibodies.
Peritumoral edema 10 46 0.1853
Strong nuclear staining was accepted as “positive,” and the
scale of positivity was evaluated according to the percentage of Dural tail sign 6 68 0.0864
positive cells. Tumors with strong staining in at least 10% were Adjacent bone invasion 5 20 0.2611
considered positive as in previous studies.17,18 The Ki-67 index was
Adjacent bone sclerosis 2 27 0.2777
used to represent the proliferative index as a percentage of posi-
tively stained cells in the most mitotically active areas. Calcification 3 19 0.9292
Gross total resection 9 99 0.0113

Imaging Studies WHO grade 2 12 17 <0.001

Magnetic resonance images were reviewed to assess the number of PGR (%) 31.9
32.2 52.2
35.9 0.0154
tumors, dural tail sign, and peritumoral edema. Tumors located in Positive PGR 14 114 0.1181
the anterior/middle cranial fossa, including the olfactory groove,
tuberculum sellae, planum sphenoidale, anterior clinoid, and ER (%) 3.2
10.3 1.7
6.3 0.3462
sphenoid ridge, cavernous sinus, petroclival/clival area, basal Positive ER 2 10 0.6985
foramina, and the petrous bone were classified as skull base. The
A P value of <0.05 was considered significant, and those values are indicated in bold.
presence of tumor calcification and changes in attached cranial
ER, estrogen receptor; PGR, progesterone receptor; WHO, World Health Organization.
bones were assessed by computed tomography.

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 ORIGINAL ARTICLE
YASUHIRO KUROI ET AL. ROLE OF PROGESTERONE RECEPTOR IN MENINGIOMAS

Table 2. Features of Meningioma and Expression Ratio of PGR and ER

PGR (%) P Value Positive ER (%) P Value

Overall 49.5
36.0 12 (7.5%)

Sex
Male 56.2
33.4 0.1978 1 (0.6%) 0.1044
Female 47.5
36.6 11 (6.8%)
Denovo tumor
Yes 51.8
36.2 0.0766 8 (5.0%) 0.1299
No 38.6
33.7 4 (2.5%)
Gynecological diseases
Yes 48.7
37.2 0.8812 9 (5.6%) 0.8195
No 49.7
35.8 3 (1.9%)
Location
Skull base 61.5
33.4 0.0009 4 (2.5%) 0.7353
Non-skull base 42.2
35.7 8 (5.0%)
Multiple
Yes 60.9
38.2 0.1979 10 (6.2%) 0.3625
No 48.3
35.7 2 (1.2%)
Peritumoral edema
Yes 46.1
34.5 0.3844 9 (5.6%) 0.4595
No 51.3
36.8 3 (1.9%)
Dural tail sign
Yes 48.9
36.9 0.8435 8 (5.0%) 0.3615
No 50.0
35.4 4 (2.5%)
Adjacent bone sclerosis
Yes 54.9
36.6 0.3786 7 (4.3%) 0.0267
No 48.3
35.9 5 (3.1%)
Adjacent bone invasion
Yes 43.2
32.6 0.3414 10 (6.2%) 0.9099
No 50.7
36.6 2 (1.2%)
Calcification
Yes 45.5
35.2 0.5706 0 (0%) 0.1520
No 50.2
36.2 12 (7.5%)
Gross total resection
Yes 48.1
37.4 0.4902 10 (6.2%) 0.2130
No 52.3
33.1 2 (1.2%)
WHO grade 2
Yes 35.5
33.6 0.0199 3 (1.9%) 0.5126
No 52.6
35.9 9 (5.6%)
Recurrent
Yes 31.9
32.2 0.0154 2 (1.2%) 0.6985
No 52.2
35.9 10 (6.2%)

A P value of <0.05 was considered significant, and those values are indicated in bold.
ER, estrogen receptor; PGR, progesterone receptor; WHO, World Health Organization.

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YASUHIRO KUROI ET AL.
A B
Recurrence-free survival
Non-skull base
Skull base
(p=0.7709)
Figure 1. Kaplan-Meier curves for RFS. There was no
difference in RFS between skull base and non-skull base
meningiomas (A). However, there was a significant
RESULTS
Characteristics of Patients and Tumors
The patient characteristics are summarized in Table 1.
One hundred and seventy-seven patients were diagnosed with
intracranial meningioma and were operated on during the study
period. Among them, 7 patients whose follow-up period was shorter
than 1 year, 4 who underwent repeated operation more than 3 times,
3 without available paraffin specimens, and 2 patients with neuro-
fibromatosis type 2 were excluded. Thus, the study included 161
meningioma specimens from 152 patients. Thirty-six patients
(23.7%) were male and 116 (76.3%) were female. The female:male
ratio was 3.22:1. The median age of the patients was 60.7
13.6
years (range, 24e86 years). Histological examination revealed WHO
grade I benign meningioma in 132 patients (82.0%), grade II me-
ningioma in 22 (13.7%), and grade III meningioma in 7 (4.4%). The
median Ki-67 index was 4.6%, and was 3.3% in grade I, 8.8% in
grade II, and 13.8% in grade III, respectively. There were significant
differences in the WHO grade and the percentage of Ki-67-positive
nuclei (P < 0.0001). Nuclear immunostaining for PGR was positive
in 128 (79.5%) and ER was positive in 12 (7.5%) patients. Sixty-one
(37.9%) were classified as having skull base meningioma and 100
(62.1%) were classified as having noneskull base meningioma.
Thirty-nine (24.2%) had convexity, 29 (18.0%) had parasagittal, 16
(9.9%) had sphenoidal, 15 (9.3%) had cerebellopontine angle, 14
(8.7%) had falx, 10 (6.2%) had tentorial, 7 (4.4%) had clinoidal, 7
(4.4%) had tuberculum sellae, 4 (2.5%) had planum sphenoidale, 3
(1.9%) had olfactory groove, 3 (1.9%) had intraventricular, 3 (1.9%)
had temporal base, 3 (1.9%) had cerebellar convexity, 2 (1.2%) had
clival, and 1 (0.6%) had foramen magnum meningioma.
There were 22 patients (28 lesions) with nonede novo menin-
gioma who had surgery or radiotherapy for the tumor before the
surgery with histopathological data for ER and PGR.
Postoperative Course
The mean postoperative follow-up period was 40.4
30.2 months.
Twenty-one tumors in 18 patients recurred during the follow-up
period. Tumors recurred in 9 of 108 (8.3%) patients with GTR and
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ORIGINAL ARTICLE
ROLE OF PROGESTERONE RECEPTOR IN MENINGIOMAS
PGR(+)
PGR(−)
(p=0.0039)
Months Months
difference between PGR-positive and -negative
meningiomas (B). PGR, progesterone receptor; RFS,
recurrence-free survival.
in 12 of 53 (22.6%) patients with STR, which was significant
(P ¼ 0.0113). Nine meningiomas (6.8%) of benign histology (WHO
grade I), 6 (27.3%) of WHO grade II, and 6 (85.7%) of WHO grade III
recurred. The Ki-67 index was significantly higher in recurrent cases
than in recurrence-free cases (9.3
8.9% vs. 3.9
4.6%,
P < 0.0001). As Ki-67 of 4.2% was previously set as a cutoff value to
predict recurrence,19 meningiomas with Ki-67 of 4.2% or over
recurred more frequently (23.1% vs. 8.3%, P ¼ 0.0090). Among the
nonede novo meningiomas, 15 of 28 tumors (13 of 19 patients)
recurred. The recurrence rate was significantly high compared with
that for de novo meningiomas (P < 0.0001).
The patients with recurrence underwent additional treatment as
follows: reoperation for 11 meningiomas in 9 patients, radio-
therapy for 3, and combined therapy for 1 patient. Five patients
died during follow-up, 4 of whom had WHO grade III malignant
meningioma and died of complication or uncontrollable tumor
regrowth. One patient with WHO grade I meningioma died of
severe acidosis due to diabetes mellitus.
Expression of PGR
The rate of positive PGR expression was 49.5
36.0% (Table 2).
PGR was positive in 128 meningiomas (79.5%). Recurrent tumors
exhibited significantly lower PGR levels than nonrecurring tumors
(31.9
32.2% vs. 52.2
35.9%, P ¼ 0.0154). PGR expression
decreased with tumor progression. PGR was positive in 52.6

35.9%, 43.7
34.0%, and 9.6
13.5% in WHO grade I, II, and
III tumors, respectively (P ¼ 0.0344). Similarly, nonede novo
meningiomas demonstrated a lower PGR expression rate than de
novo meningiomas (38.6
33.7% vs. 51.8
36.2%, P ¼ 0.0056).
This suggests that low PGR expression is a factor for poor prog-
nosis, reflecting increased tumor progression and recurrence. Of
note, skull base meningiomas had significantly higher PGR
expression than noneskull base meningiomas (61.5
33.4% vs.
42.2
35.7%, P ¼ 0.0009).
Expression of ER
The median ER-positive rate was 1.9
7.0%, with the majority of
tumors being negative (Table 2). Twelve meningiomas (7.5%) were
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 ORIGINAL ARTICLE
YASUHIRO KUROI ET AL. ROLE OF PROGESTERONE RECEPTOR IN MENINGIOMAS

ER positive. There was no correlation between the expression of Prognostic Value of ER

ER and PGR (r ¼ 0.01358, P ¼ 0.8643 by correlation ER was previously considered to be unrelated to prognosis.
coefficients analysis). However, in a recent study on a large number of WHO grade III
ER expression was higher in malignant meningiomas (WHO meningioma cases, only 8% were PGR-positive, and 41.7%
grade II or III) (4.0
11.3% vs. 1.5
5.5%, P ¼ 0.0774). exhibited positive ER expression, which is correlated with poor
Compared with de novo meningiomas, ER expression in nonede prognosis.18 In our series, positive ER expression and tumor
novo meningiomas was significantly high (4.1
1.3% vs. 1.4
progression were not significantly correlated, probably due to
0.6%, P ¼ 0.0345). Therefore, higher ER expression may indicate the small sample size of malignant meningiomas. Our data were
poor prognosis. However, the ER expression ratio between partially consistent with this idea because nonede novo menin-
recurrent and nonrecurring tumors was not significant (3.2
10.3 giomas had significantly high ER expression.
vs. 1.7
6.3%, P ¼ 0.3462).
Benign Biology of Skull Base Meningiomas
Analysis of Recurrence-free Survival Skull base meningiomas are generally considered to be biologi-
Factors for short RFS were as follows: nonede novo (P < 0.0001), cally benign.15,16,22 Skull base meningiomas are reported to be
negative PGR (P ¼ 0.0176), Ki-67 4.2% (P ¼ 0.0123), WHO grade associated with a lower proliferation index, and higher likelihood
II or III (P < 0.0001), STR (P ¼ 0.0195), multiple tumors of WHO grade I23 and lower Ki-67 indices.14 Preserving Karnofsky
(P ¼ 0.0162), and absent dural tail sign (P ¼ 0.0384). On the other Performance Status (KPS) of the patient is the most crucial factor
hand, the following factors were not significant: ER expression for patients with skull base meningioma. Nakao et al24
(P ¼ 0.6106), peritumoral edema (P ¼ 0.2760), sex (P ¼ 0.4454), demonstrated that skull base meningiomas are controllable, in
calcification (P ¼ 0.9325), bone sclerosis (P ¼ 0.2173), bone the context of preserving KPS, if appropriate additional surgery
invasion (P ¼ 0.3405), located in skull base (P ¼ 0.6422), and or radiotherapy is applied at the time of first recurrence. For
gynecological disease (P ¼ 0.4280). The Kaplan-Meier analysis of
RFS by PGR and tumor location is shown in Figure 1. Table 3. Skull Base Meningiomas and Non-skull base
Meningiomas
Postoperative Course of Skull Base Meningioma Patients Skull Base Non-skull
Sixty-one patients (37.9%) had skull base meningiomas (n [ 61) base (n [ 100) P Value
(Table 3). Compared with noneskull base tumors, skull base
meningiomas were difficult to remove entirely. Of the skull base Sex (female) 49 75 0.4357
meningioma patients, 50.8% (31 of 61) underwent GTR, whereas Age (years) 62.0
14.5 60.0
13.0 0.3654
77.0% of the noneskull base meningioma patients (77 of 100) Recurrence 9 12 0.6356
underwent GTR (P ¼ 0.0006). There was no significant
difference in WHO grade or Ki-67 index between skull base and RFS (years) 14.1 17 0.7709
noneskull base meningiomas. Nevertheless, skull base menin- Ki-67 (%) 4.2
5.7 4.8
5.6 0.5275
giomas demonstrated a similar prognosis with noneskull base Ki-67  4.2% 15 37 0.1024
meningiomas.
Denovo tumor 48 85 0.3054
WHO grade II or III 8 21 0.2066
DISCUSSION
Multiple 4 11 0.3468
Many studies have examined the roles of ER and PGR in menin-
Gynecological disease 12 24 0.5226
gioma to assess their ability as prognostic markers in predicting
the behavior of meningioma. Peritumoral edema 18 38 0.2724
Dural tail sign 21 53 0.0218
PGR Is a Favorable Prognostic Factor Adjacent bone invasion 12 13 0.2568
PGR is considered to correlate with prognosis because patients Adjacent bone sclerosis 13 16 0.3949
with meningioma positive for PGR expression have a good prog-
Gross total resection 31 77 0.0006
nosis, and PGR decreases during tumor progression.11,17
In our study, benign meningioma patients (WHO grade I) had Calcification 8 14 0.8739
higher PGR expression, consistent with previous reports.7,11 To PGR (%) 61.5
33.4 42.2
35.7 0.0009
our knowledge, there is no report on the relationship between
Positive PGR 55 73 0.0089
skull base location and PGR expression. One previous study found
that PGR-positive meningiomas were more common in the skull ER (%) 1.3
6.2 2.3
7.4 0.3899
base, but there was no discussion of the data.20 The etiology of the Positive ER 4 8 0.7353
relationship between PGR expression and tumor progression is
A P value of <0.05 was considered significant, and those values are indicated in bold.
unclear, but it may be due to the higher rate of mitosis in
ER, estrogen receptor; PGR, progesterone receptor; RFS, recurrent free survival; WHO,
tumor cells and an increase in angiogenesis with low PGR
World Health Organization.
expression.21

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 ORIGINAL ARTICLE
YASUHIRO KUROI ET AL. ROLE OF PROGESTERONE RECEPTOR IN MENINGIOMAS

skull base meningiomas, STR patients with adjuvant radiotherapy
had a similar prognosis as GTR patients.25
Currently, the principal aim of surgical management is maximum
resection with minimal neurological deficits. Before the studies
mentioned above, our group found that a noneskull base location
was an independent predictor of a high Ki-67 index and tumor
growth.16 Furthermore, comparing skull base and noneskull base
meningiomas with postoperative gamma knife radiosurgery, skull
base meningiomas demonstrated a significantly longer RFS after
treatment.26 Therefore, for small tumors that are firmly attached to
the eloquent structures, maximum resection is of the utmost
importance. In our study, the rate of GTR in skull base
meningiomas was 50%, whereas that in noneskull base meningi-
omas was 77%. Although there are previous reports of higher GTR
rates, we believe that our strategy is sufficient. Excluding some
exceptions, almost all patients with skull base meningioma main-
tained a KPS >70 during the postoperative follow-up.
studies. One reason for this is that we excluded patients without ER/
PGR data, the majority of whom were operated on more than 10
years ago and have long follow-up periods. However, in our study,
we demonstrated that lower expression of PGR was a poor prog-
nostic factor. Furthermore, skull base meningiomas frequently
exhibited high PGR expression. Some studies found no difference
in PGR expression between skull base and noneskull base
meningiomas.23 A lack of standardized methods for
immunostaining, heterogeneity of tumor regions, and other
issues with assessment of staining pattern are the likely
explanation. We assessed the expression of PGR as not merely
positive or negative, but with an exact percentage, which enabled
us to clarify its prognostic value for the period of RFS. The
postoperative course of skull base meningioma is highly
influenced by the extent of resection, which may explain the
variation in recurrence rates among previous reports.

Limitations
There are several limitations in our study. First, this was a retro-
spective study at a single institute. Therefore, almost all patients
were Japanese and the number of the cases was limited. Second, we
did not assess somatic tumor mutations, which may affect tumor
characteristics or behavior. Third, the follow-up period was 3e4
years, which is short compared with that in other retrospective
CONCLUSIONS
In our study, negative PGR was a prognostic factor for poor
prognosis. PGR expression decreased with recurrence or
regrowth. ER expression may be a prognostic factor, but we were
unable to confirm this due to the limited number of malignant
meningiomas. High PGR expression may play a role in the benign
biology of skull base meningiomas.

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WORLD NEUROSURGERY -: e1-e7, - 2018
ORIGINAL ARTICLE
ROLE OF PROGESTERONE RECEPTOR IN MENINGIOMAS
25. Ohba S, Kobayashi M, Horiguchi T, Onozuka S, commercial or financial relationships that could be construed
Yoshida K, Ohira T. Long-term surgical outcome as a potential conflict of interest.
and biological prognostic factors in patients with
Received 27 April 2018; accepted 11 July 2018
skull base meningiomas. J Neurosurg. 2011;114:
1278-1287. Citation: World Neurosurg. (2018).
https://doi.org/10.1016/j.wneu.2018.07.100
26. Nakaya K, Chernov M, Kasuya H, Izawa M,
Journal homepage: www.WORLDNEUROSURGERY.org
Hayashi M, Kato K, et al. Risk factors for
regrowth of intracranial meningiomas after Available online: www.sciencedirect.com
gamma knife radiosurgery: importance of the 1878-8750/$ - see front matter ª 2018 Elsevier Inc. All
histopathological grade and MIB-1 index. Minim rights reserved.
Invasive Neurosurg. 2009;52:216-221.
Conflict of interest statement: The authors declare that the
article content was composed in the absence of any
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