Progesterone and estrogen receptors in meningiomas: prognostic considerations

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✓ Meningiomas often contain steroid hormone receptors, but the correlation of receptor presence with patient outcome or mitotic index is unclear. Intracranial meningiomas from 70 patients (27 males and 43 females, mean age 52.9 + 1.7 years [mean ± standard error of the mean], range 15–78 years) were evaluated immunocytochemically for female sex hormone receptors using specific monoclonal antibodies. Prognostic correlations were determined using statistical analyses that included clinical and histological variables. Twenty-eight tumors were benign, 27 had atypical features, and 15 were malignant. Thirty tumors were meningotheliomatous, 11 were fibroblastic, 28 were transitional, and one was secretory. Twenty-nine of the 70 primary tumors recurred (mean interval to recurrence 50.1 ± 10 months). The mean progression-free follow-up period for patients without recurrence was 82.1 ± 7.7 months. Nuclear staining for the progesterone receptor (PR) was found in 58 cases (83%) and PR status was scored as 0 (0% nuclei positive), 1 (< 1%), 2 (1–9%), 3 (10–49%), or 4 (> 50%). Only six tumors (8.6%) contained nuclear estrogen receptor (ER) staining, which was limited to a small number of nuclei (< 1%). Fisher's exact test (two-tailed) showed an inverse correlation between tumor grade and PR staining score (p ≤ 0.001), with 96% of benign and 40% of malignant meningiomas containing PR-positive nuclei. No correlation between age or histological subtype and PR score was detected. Meningiomas from female patients had more PRs (p ≤ 0.05). Analysis of variance revealed that the mitotic index (total counts of mitoses per 10 high-power fields) for tumors with 0 PR staining (18 ± 4.4) was higher (p ± 0.0001) than for those with PR scores of 1 to 4 (4.3 ± 1.9, 5.1 ± 2, 2.2 ± 0.8, and 1.7 ± 0.9, respectively). Univariate analysis indicated that the absence of PR, high mitotic index, and higher tumor grade were significant factors for shorter disease-free intervals. Multivariate analysis showed that a three-factor interaction model, with a PR score of 0, mitotic index greater than 6, and malignant tumor grade, was a highly significant predictor (p ≤ 0.0001) for worse outcome in patients harboring meningiomas. These data indicate that the presence of PRs, even in a small number of tumor cells, is a favorable prognostic factor for meningiomas.

Article Information

Address reprint requests to: Dora W. Hsu, M.S., Neuropathology, Warren 3, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts 02114.

© AANS, except where prohibited by US copyright law.

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Figures

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    Photomicrographs showing the results of PR immunostaining. a: Benign meningioma with approximately one-half of its nuclei displaying positive reaction for the receptor. The tissue was given a score of 4 for the PR status. b: The same benign meningioma shown at higher magnification. The specific progesterone receptor staining is limited to nuclei. c: A malignant meningioma that has a totally negative response to PR immunostaining. Note the area of necrosis shown on the right side of the panel and the sheeting of tumor cells. d: The same malignant meningioma shown at higher magnification demonstrates numerous mitotic figures (arrows) and cells with prominent nucleoli. Avidin-biotinimmunoperoxidase complex, hematoxylin counterstain. a and c: original magnification × 200; b and d: original magnification × 400.

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    Bar graph demonstrating the correlation between mitotic indices and the PR status of meningiomas. The mitotic index for meningiomas with a negative PR status (PR = 0) is significantly higher than the mitotic index for PR-positive meningiomas (PR = 1–4) (p ≤ 0.0001). Least square means methods of ANOVA.

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    Kaplan—Meier survival curves. Upper Left: Groups of meningiomas defined by tumor grade. The difference between malignant and benign groups is significant (log-rank test, p ≤ 0.015). Upper Right: Groups of meningiomas defined by mitotic index (≤ 6 or > 6). The difference between groups is highly significant (log-rank test, p ≤ 0.0001). Lower Left: Groups of meningiomas defined by PR status (PR-positive [scores 1–4] vs. PR-negative [score 0]). Patients with PR scores 1 to 4 had a significantly longer progression-free survival than those with PR score 0 (log-rank test, p ≤ 0.0001). Lower Right: Groups of meningiomas defined by histological subtype. Patients with tumors of the meningotheliomatous type had a shorter duration of progression-free survival. n = number of cases.

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