High p-mTOR expression is associated with recurrence and shorter disease-free survival in atypical meningiomas

被引:11
作者
Barresi, Valeria [1 ,3 ]
Lionti, Simona [1 ]
La Rocca, Lilli [1 ]
Caliri, Samuel [1 ]
Caffo, Maria [2 ]
机构
[1] Univ Messina, Dept Pathol Adulthood & Evolut Age, Messina, Italy
[2] Univ Messina, Dept Biomed & Odontoiatr Sci & Morphol & Funct Im, Messina, Italy
[3] Univ Verona, Dept Diagnost & Publ Hlth, Verona, Italy
关键词
atypical meningioma; PI3K/AKT; p-mTOR; prognosis; therapy; MAMMALIAN TARGET; ACTIVATION; CANCER; PATHWAYS; GROWTH;
D O I
10.1111/neup.12524
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Due to their widely variable clinical behavior, the post-surgical treatment of atypical meningiomas is controversial. Therefore, prognostic factors able to identify high-risk cases, which may benefit from adjuvant treatments, are warranted. Mammalian target of rapamycin (mTOR) belongs to the PI3K-AKT pathway. Its phosphorylated form (p-mTOR Ser2448) is involved in cell growth, differentiation and tumorigenesis. The aim of this study was to evaluate p-mTOR Ser2448 expression and its eventual correlation with clinicopathological features, recurrence, or disease-free survival (DFS), in atypical meningiomas. p-mTOR immunohistochemical expression was analyzed in 48 atypical meningiomas and correlated with clinicopathological parameters and with DFS. Eighty-one percent of atypical meningiomas expressed p-mTOR Ser2448. High immuno-expression was significantly associated with recurrences (P = 0.01) and lower DFS (P = 0.01). The presence of brain invasion, high mitotic index plus sheeting, and Simpson grade were significant and independent prognostic variables at multivariate analysis. p-mTOR Ser2448 is expressed in atypical meningiomas. High expression predicts development of recurrences and shorter DFS in patients affected by these tumors. Since p-mTOR Ser2448 is a target of anti-neoplastic drugs, evaluation of its expression may be used, not only to identify atypical meningiomas at higher risk of recurrence, but also to select those to submit to adjuvant targeted chemotherapy.
引用
收藏
页码:22 / 29
页数:8
相关论文
共 32 条
[1]   Extent of Resection and Overall Survival for Patients With Atypical and Malignant Meningioma [J].
Aizer, Ayal A. ;
Bi, Wenya Linda ;
Kandola, Manjinder S. ;
Lee, Eudocia Q. ;
Nayak, Lakshmi ;
Rinne, Mikael L. ;
Norden, Andrew D. ;
Beroukhim, Rameen ;
Reardon, David A. ;
Wen, Patrick Y. ;
Al-Mefty, Ossama ;
Arvold, Nils D. ;
Dunn, Ian F. ;
Alexander, Brian M. .
CANCER, 2015, 121 (24) :4376-4381
[2]   Histopathological features to define atypical meningioma: What does really matter for prognosis? [J].
Barresi, Valeria ;
Lionti, Simona ;
Caliri, Samuel ;
Caffo, Maria .
BRAIN TUMOR PATHOLOGY, 2018, 35 (03) :168-180
[3]   Classification of Human Meningiomas: Lights, Shadows, and Future Perspectives [J].
Barresi, Valeria ;
Caffo, Maria ;
Tuccari, Giovanni .
JOURNAL OF NEUROSCIENCE RESEARCH, 2016, 94 (12) :1604-1612
[4]   Embolized meningiomas: risk of overgrading and neo-angiogenesis [J].
Barresi, Valeria ;
Branca, Giovanni ;
Granata, Francesca ;
Alafaci, Concetta ;
Caffo, Maria ;
Tuccari, Giovanni .
JOURNAL OF NEURO-ONCOLOGY, 2013, 113 (02) :207-219
[5]   A high-throughput kinome screen reveals serum/glucocorticoid-regulated kinase 1 as a therapeutic target for NF2-deficient meningiomas [J].
Beauchamp, Roberta L. ;
James, Marianne F. ;
DeSouza, Patrick A. ;
Wagh, Vilas ;
Zhao, Wen-Ning ;
Jordan, Justin T. ;
Stemmer-Rachamimov, Anat ;
Plotkin, Scott R. ;
Gusella, James F. ;
Haggarty, Stephen J. ;
Ramesh, Vijaya .
ONCOTARGET, 2015, 6 (19) :16981-16997
[6]   Phosphorylated Mammalian Target of Rapamycin p-mTOR Is a Favorable Prognostic Factor than mTOR in Gastric Cancer [J].
Cao, Guo-dong ;
Xu, Xing-yu ;
Zhang, Jia-wei ;
Chen, Bo ;
Xiong, Mao-ming .
PLOS ONE, 2016, 11 (12)
[7]   WHO grade II and III meningiomas: a study of prognostic factors [J].
Durand, Anne ;
Labrousse, Francois ;
Jouvet, Anne ;
Bauchet, Luc ;
Kalamarides, Michel ;
Menei, Philippe ;
Deruty, Robert ;
Moreau, Jean Jacques ;
Fevre-Montange, Michelle ;
Guyotat, Jacques .
JOURNAL OF NEURO-ONCOLOGY, 2009, 95 (03) :367-375
[8]   Lesion-targeted thrombopoietin potentiates vasculogenesis by enhancing motility and enlivenment of transplanted endothelial progenitor cells via activation of Akt/mTOR/p70S6kinase signaling pathway [J].
Eguchi, Masamichi ;
Masuda, Haruchika ;
Kwon, Sangmon ;
Shirakura, Katsuya ;
Shinno, Tomoko ;
Ito, Rie ;
Kobori, Michiru ;
Asahara, Takayuki .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 2008, 45 (05) :661-669
[9]   Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development [J].
El-Habr, Elias A. ;
Levidou, Georgia ;
Trigka, Eleni-Andriana ;
Sakalidou, Joanna ;
Piperi, Christina ;
Chatziandreou, Ilenia ;
Spyropoulou, Anastasia ;
Soldatos, Rigas ;
Tomara, Georgia ;
Petraki, Kalliopi ;
Samaras, Vassilis ;
Zisakis, Athanasios ;
Varsos, Vassilis ;
Vrettakos, George ;
Boviatsis, Efstathios ;
Patsouris, Efstratios ;
Saetta, Angelica A. ;
Korkolopoulou, Penelope .
VIRCHOWS ARCHIV, 2014, 465 (04) :473-485
[10]   WHO grade 1 meningioma recurrence: Are location and Simpson grade still relevant? [J].
Gallagher, Mathew J. ;
Jenkinson, Michael D. ;
Brodbelt, Andrew R. ;
Mills, Samantha J. ;
Chavredakis, Emmanuel .
CLINICAL NEUROLOGY AND NEUROSURGERY, 2016, 141 :117-121