Recurrence/Regrowth in Grade I Meningioma: How to Predict?

Abstract

The HLA-G and HLA-E molecules, Ki67, progesterone (PR), estrogen (ER) and androgen receptors (AR), p53, COX-2, and HER2 were studied to assess whether the biological behavior of grade I meningiomas is related to their expression. Tissue samples from 96 patients with grade I intracranial meningiomas were analyzed by immunohistochemistry on tissue microarray blocks (TMA) using antibodies specific for HLA-G, HLA-E, Ki67, PR, ER, AR, p53, COX-2, and HER2. Meningiomas were classified as small (≤2 cm, 1.0%), medium (>2 and ≤4 cm, 32.3%), and large (>4 cm, 66.7%). Tumor size was not related to recurrence/regrowth (p = 0.486), but was significantly correlated with peritumoral edema (p = 0.031) and intratumoral calcifications (p = 0.018). Recurrent meningiomas were observed in 14.6% of cases. Immunostaining for each marker was: HLA-G 100%; HLA-E 95.6%; PR 62%; ER 2.1%; AR 6.5%; p53 92.6%; COX-2 100%; HER2 0%; Ki67, mean 2.61 ± 2.29%, median 2.1%. Primary and recurrent meningiomas showed no significant relation with HLA-E and hormone receptors (p > 0.05), except for Ki67, where a higher median was observed in recurrent tumors than in primary (p = 0.014). The larger the tumor, the more severe the peritumoral edema, and the greater the presence of calcifications. Ki67 appears to be a good biomarker of recurrence/regrowth in grade I meningiomas.

Progesterone Receptor Expression in Meningiomas: Pathological and Prognostic Implications

“…Fourteen reviewed studies focused on PR expression and recurrence of meningiomas; seven have found significant inverse correlation, with high recurrence rates in meningiomas with low PR expression at initial surgery (10-14, 23, 29). On the other hand, other studies (21,26,31,33,35,36,39) did not find significant results. Like our previous report (10), the present study confirms the inverse correlation between PR values and recurrence (p = 0.0004); the high PR expression (≥80%) is a single efficient predictive factor (p = 0.017).…”

“…Among the 24 studies including all WHO grades, the correlation between PR expression and WHO grade was studied in 16; 12 found significantly higher rate of cases with high PR expression in benign WHO I tumors and low expression in atypical WHO II ones (8,12,13,19,20,24,27,28,30,34,36,37) (Table 9). The correlation between PR expression and Ki67 MIB-1 was studied in 10 reviewed series; 5 (12,19,22,24,34) found significantly lower PR expression in meningiomas with higher Ki67-Li; on the other hand, others (23,30,33,36,39) did not find significant differences.…”

“…The score and cut-off values of PR expression have variably been considered in the reviewed reports. Many studies (11,13,17,21,26,31,39) only report negative or positive expression. Others consider as positive only those cases with strong staining in >10% or moderate staining in >50% (12,34,37).…”

“…The correlation between PR expression and pathological findings of meningiomas has largely been discussed, but the reported results are controversial. Among the 30 reviewed studies (Table 9), six only included benign WHO grade I meningiomas (11,14,21,23,33,39); thus the significance of the WHO grade was not possible. Among the 24 studies including all WHO grades, the correlation between PR expression and WHO grade was studied in 16; 12 found significantly higher rate of cases with high PR expression in benign WHO I tumors and low expression in atypical WHO II ones (8,12,13,19,20,24,27,28,30,34,36,37) (Table 9).…”

HLA-G and Other Immune Checkpoint Molecules as Targets for Novel Combined Immunotherapies

“…The expression of HLA-G and its role in cancer progression has been addressed in gliomas [ 100 , 101 ], glioblastoma [ 102 , 103 ], and Ewing sarcoma [ 104 , 105 , 106 ], whereas limited information is available on meningioma [ 107 ], retinoblastoma [ 108 ], and other sarcomas [ 73 ].…”