Meningiomas Display a Specific Immunoexpression Pattern in a Rostrocaudal Gradient: An Analysis of 366 Patients

Abstract

BACKGROUND: Meningiomas are heterogeneous, with differences in anatomical, histopathological, and clinical characteristics. Such spatial variability in meningioma biology is thought to result from differences in the expression of critical developmental regulators. We hypothesized that the variability in meningioma biology would follow gradients such as in embryology and tested a cohort of 366 meningiomas for histopathological and immunohistochemical gradients. METHODS: The medical records from 366 patients treated for meningiomas from 2003 to 2016 were retrospectively analyzed for age, gender, anatomical localization, recurrence-free survival, overall survival, histopathological diagnosis, and immunohistochemistry findings for 6 markers: epithelial membrane antigen (EMA), progesterone receptor (PR), CD34, S100, p53, and Ki-67 labeling index. RESULTS: EMA, PR, S100, p53, and CD34 were expressed in 94%, 73%, 49%, 26%, and 23% of the tumors, respectively. p53 expression correlated positively with Ki-67 and World Health Organization (WHO) grade (r(tau) = 0.31 and r(tau) = 0.4, respectively). PR positivity correlated inversely with S100, p53, Ki-67, and WHO grade (r(tau) = -0.19, r(tau) = -0.14, r(tau) = -0.15, and r(tau) = -0.16, respectively). All secretory meningiomas were positive for EMA and PR and negative for S100, and this pattern exhibited a rostrocaudal gradient. The overall proportion of EMA(+)PR(+)S100(-) cases was significantly lower in the cranial vault (30.3%) than in the skull base (45.89%; P = 0.021). The proportion of WHO grade II-III tumors was greater in cranial vault than in skull base meningiomas. CONCLUSIONS: Unsupervised methods detected an association between the anatomical location and tumor biology in meningiomas. Unlike the categorical associations that former studies had indicated, the present study revealed a rostrocaudal gradient in both the cranial vault and the skull base, correlating with human developmental biology.