Biom-54. validating mcm2 immunohistochemistry as a surrogate marker for aggressive meningioma

Abstract Increasing efforts have focused to improve meningioma classification through various multi-omic analyses. One such recent study (Nassiri, et al, Nature, 2021) proposed an integrative molecular classification for meningiomas that included 4 molecular subtypes (MG1-4), with possible immunohistochemical surrogates for each subtype including S100B, ACADL, SCGN, and MCM2, respectively. While these immunohistochemical surrogates have been proposed for meningioma risk-stratification, their clinical utility has not been thoroughly tested. In this study, we sought to evaluate the utility of these immunohistochemical markers for risk-stratification in an independent cohort of meningioma. Tissue microarrays containing meningioma tissues were constructed, immunohistochemically stained, and blindly scored. Our cohort included n = 142 tumors (CNS WHO: 1=93, 2=45, 3=4). Median age was 49 years (range 14-80 years) with 89 female and 53 male patients. We found that MCM2 immunopositivity was a univariate marker of poor prognosis (median progression-free survival 1.2 years) when compared to negative tumors (median progression-free survival 13.0 years). The other three markers (S100B, ACADL, SCGN) were not associated with survival. MCM2 staining held up as a significantly independent (p = 0.03) poor prognostic marker on multivariate Cox proportional hazard modeling including other histopathological features: CNS WHO grade, brain invasion, mitotic index, and tumor size. Although MCM2 staining was independent of CNS WHO grade, all 4 of the CNS WHO 3 meningiomas were positive for MCM2. MCM2-positive tumors had a higher average mitotic count (6.1 mitoses/10hpf) compared to MCM2-negative tumors (1.8 mitoses/10hpf) (p = 0.0002, two-tailed t test). There was no difference between MCM2-positive and MCM2-negative meningiomas in relation to maximum tumor size (4.9cm and 4.2cm, respectively) and mean age (51.71 years and 50.34 years, respectively). In summary, in our cohort we found MCM2 immunopositive staining (surrogate marker for high-risk molecular subtype M4) to be an independently poor prognostic biomarker in meningioma when accounting for other well-established histopathological characteristics.