TY - JOUR
T1 - Paths of Evolution of Progressive Anaplastic Meningiomas: A Clinical and Molecular Pathology Study
AU - Di Bonaventura, Rina
AU - Lauretti, Liverana
AU - Martini, Maurizio
AU - Cenci, Tonia
AU - Di Monaco, Giuliano
AU - Palombi, Davide
AU - Ceccarelli, Giovanni Maria
AU - Chiesa, Silvia
AU - Gessi, Marco
AU - Granitto, Alessia
AU - Albanese, Alessio
AU - Larocca, Luigi Maria
AU - D'Alessandris, Quintino Giorgio
AU - Pallini, Roberto
AU - Olivi, Alessandro
PY - 2023
Y1 - 2023
N2 - Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.
AB - Grade 3 meningiomas are rare malignant tumors that can originate de novo or from the progression of lower grade meningiomas. The molecular bases of anaplasia and progression are poorly known. We aimed to report an institutional series of grade 3 anaplastic meningiomas and to investigate the evolution of molecular profile in progressive cases. Clinical data and pathologic samples were retrospectively collected. VEGF, EGFR, EGFRvIII, PD-L1; and Sox2 expression; MGMT methylation status; and TERT promoter mutation were assessed in paired meningioma samples collected from the same patient before and after progression using immunohistochemistry and PCR. Young age, de novo cases, origin from grade 2 in progressive cases, good clinical status, and unilateral side, were associated with more favorable outcomes. In ten progressive meningiomas, by comparing molecular profile before and after progression, we identified two subgroups of patients, one defined by Sox2 increase, suggesting a stem-like, mesenchymal phenotype, and another defined by EGFRvIII gain, suggesting a committed progenitor, epithelial phenotype. Interestingly, cases with Sox2 increase had a significantly shortened survival compared to those with EGFRvIII gain. PD-L1 increase at progression was also associated with worse prognosis, portending immune escape. We thus identified the key drivers of meningioma progression, which can be exploited for personalized treatments.
KW - EGFRvIII
KW - PD-L1
KW - Sox2
KW - anaplastic
KW - meningioma
KW - progression
KW - EGFRvIII
KW - PD-L1
KW - Sox2
KW - anaplastic
KW - meningioma
KW - progression
UR - http://hdl.handle.net/10807/271854
U2 - 10.3390/jpm13020206
DO - 10.3390/jpm13020206
M3 - Article
SN - 2075-4426
VL - 13
SP - 206
EP - 206
JO - Journal of Personalized Medicine
JF - Journal of Personalized Medicine
ER -