{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T13:32:40Z","timestamp":1751463160806,"version":"3.40.5"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T00:00:00Z","timestamp":1543795200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Due to their widely variable clinical behavior, the post\u2010surgical treatment of atypical meningiomas is controversial. Therefore, prognostic factors able to identify high\u2010risk cases, which may benefit from adjuvant treatments, are warranted. Mammalian target of rapamycin (mTOR) belongs to the PI3K\u2010AKT pathway. Its phosphorylated form (p\u2010mTOR Ser2448) is involved in cell growth, differentiation and tumorigenesis. The aim of this study was to evaluate p\u2010mTOR Ser2448 expression and its eventual correlation with clinicopathological features, recurrence, or disease\u2010free survival (DFS), in atypical meningiomas. p\u2010mTOR immunohistochemical expression was analyzed in 48 atypical meningiomas and correlated with clinicopathological parameters and with DFS. Eighty\u2010one percent of atypical meningiomas expressed p\u2010mTOR Ser2448. High immuno\u2010expression was significantly associated with recurrences (<jats:italic>P<\/jats:italic> = 0.01) and lower DFS (<jats:italic>P<\/jats:italic> = 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\u2010mTOR Ser2448 is expressed in atypical meningiomas. High expression predicts development of recurrences and shorter DFS in patients affected by these tumors. Since p\u2010mTOR Ser2448 is a target of anti\u2010neoplastic 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.<\/jats:p>","DOI":"10.1111\/neup.12524","type":"journal-article","created":{"date-parts":[[2018,12,4]],"date-time":"2018-12-04T03:26:03Z","timestamp":1543893963000},"page":"22-29","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["High p\u2010mTOR expression is associated with recurrence and shorter disease\u2010free survival in atypical meningiomas"],"prefix":"10.1111","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7086-1920","authenticated-orcid":false,"given":"Valeria","family":"Barresi","sequence":"first","affiliation":[{"name":"Departments of Pathology in Adulthood and Evolutive Age University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Lionti","sequence":"additional","affiliation":[{"name":"Departments of Pathology in Adulthood and Evolutive Age University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilli","family":"La Rocca","sequence":"additional","affiliation":[{"name":"Departments of Pathology in Adulthood and Evolutive Age University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel","family":"Caliri","sequence":"additional","affiliation":[{"name":"Departments of Pathology in Adulthood and Evolutive Age University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Caffo","sequence":"additional","affiliation":[{"name":"Biomedical and Odontoiatric Sciences, and of Morphological and Functional Images University of Messina  Messina Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,12,3]]},"reference":[{"key":"e_1_2_7_2_1","first-page":"ii1","article-title":"CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2006\u20132010","volume":"2","author":"Ostrom QT","year":"2013","journal-title":"Neuro Oncol Suppl"},{"key":"e_1_2_7_3_1","first-page":"232","volume-title":"WHO Classification of Tumours of the Central Nervous System","author":"Perry A","year":"2016"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29639"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clineuro.2016.01.006"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.20.1.22"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199712000-00008"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-009-9934-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30321-7"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1974"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.soc.2013.06.008"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10912"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/7082696"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-07-4719"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-54490-3_23"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10014-018-0318-z"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-443-06982-6.00010-9"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-013-1117-3"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-008-9746-7"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-1904"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nox018"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-014-1641-3"},{"key":"e_1_2_7_23_1","article-title":"Phosphorylated mTOR expression profiles in human Normal and carcinoma tissues","volume":"1397063","author":"Lee H","year":"2017","journal-title":"Dis Markers"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2008.08.002"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2014.10.001"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01581-08"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23801"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168085"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.24732"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-08345-8"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3025"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.2967\/jnumed.111.089623"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.4858"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fneup.12524","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12524","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T02:19:24Z","timestamp":1694657964000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,3]]},"references-count":32,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,2]]}},"alternative-id":["10.1111\/neup.12524"],"URL":"https:\/\/doi.org\/10.1111\/neup.12524","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"type":"print","value":"0919-6544"},{"type":"electronic","value":"1440-1789"}],"subject":[],"published":{"date-parts":[[2018,12,3]]},"assertion":[{"value":"2018-07-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-10-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-12-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}