{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T16:31:08Z","timestamp":1769099468647,"version":"3.49.0"},"reference-count":22,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,2]],"date-time":"2021-10-02T00:00:00Z","timestamp":1633132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100012940","name":"Universit\u00e4tsklinikum T\u00fcbingen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012940","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neurosurg Rev"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The expression of somatostatin receptors in meningioma is well established. First, suggestions of a prognostic impact of SSTRs in meningioma have been made. However, the knowledge is based on few investigations in small cohorts. We recently analyzed the expression of all five known SSTRs in a large cohort of over 700 meningiomas and demonstrated significant correlations with WHO tumor grade and other clinical characteristics. We therefore expanded our dataset and additionally collected information about radiographic tumor recurrence and progression as well as clinically relevant factors (gender, age, extent of resection, WHO grade, tumor location, adjuvant radiotherapy, neurofibromatosis type 2, primary\/recurrent tumor) for a comprehensive prognostic multivariate analysis (<jats:italic>n<\/jats:italic>\u2009=\u2009666). The immunohistochemical expression scores of SSTR1, 2A, 3, 4, and 5 were scored using an intensity distribution score ranging from 0 to 12. For recurrence-free progression analysis, a cutoff at an intensity distribution score of 6 was used. Univariate analysis demonstrated a higher rate of tumor recurrence for increased expression scores for SSTR2A, SSTR3, and SSTR4 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0312, <jats:italic>p<\/jats:italic>\u2009=\u20090.0351, and <jats:italic>p<\/jats:italic>\u2009=\u20090.0390, respectively), while high expression levels of SSTR1 showed less frequent tumor recurrences (<jats:italic>p<\/jats:italic>\u2009=\u20090.0012). In the Kaplan\u2013Meier analysis, a higher intensity distribution score showed a favorable prognosis for SSTR1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0158) and an unfavorable prognosis for SSTR2A (0.0143). The negative prognostic impact of higher SSTR2A expression remained a significant factor in the multivariate analysis (RR 1.69, <jats:italic>p<\/jats:italic>\u2009=\u20090.0060). We conclude that the expression of SSTR2A has an independent prognostic value regarding meningioma recurrence.<\/jats:p>","DOI":"10.1007\/s10143-021-01651-w","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T18:39:03Z","timestamp":1633372743000},"page":"2671-2679","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The immunohistochemical expression of SSTR2A is an independent prognostic factor in meningioma"],"prefix":"10.1007","volume":"45","author":[{"given":"Christina","family":"Fodi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Skardelly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann-Martin","family":"Hempel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elgin","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salvador","family":"Castaneda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghazaleh","family":"Tabatabai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Honegger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcos","family":"Tatagiba","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"Schittenhelm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1083-1276","authenticated-orcid":false,"given":"Felix","family":"Behling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,10,2]]},"reference":[{"key":"1651_CR1","doi-asserted-by":"publisher","first-page":"v1","DOI":"10.1093\/neuonc\/noz150","volume":"21","author":"QT Ostrom","year":"2019","unstructured":"Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, Barnholtz-Sloan JS (2019) CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2012\u20132016. Neuro Oncol 21:v1\u2013v100. https:\/\/doi.org\/10.1093\/neuonc\/noz150","journal-title":"Neuro Oncol"},{"key":"1651_CR2","doi-asserted-by":"publisher","first-page":"e383","DOI":"10.1016\/S1470-2045(16)30321-7","volume":"17","author":"R Goldbrunner","year":"2016","unstructured":"Goldbrunner R, Minniti G, Preusser M, Jenkinson MD, Sallabanda K, Houdart E, von Deimling A, Stavrinou P, Lefranc F, Lund-Johansen M, Moyal EC, Brandsma D, Henriksson R, Soffietti R, Weller M (2016) EANO guidelines for the diagnosis and treatment of meningiomas. Lancet Oncol 17:e383-391. https:\/\/doi.org\/10.1016\/S1470-2045(16)30321-7","journal-title":"Lancet Oncol"},{"key":"1651_CR3","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41598-019-57254-5","volume":"10","author":"JM Lemee","year":"2020","unstructured":"Lemee JM, Corniola MV, Meling TR (2020) Benefits of re-do surgery for recurrent intracranial meningiomas. Sci Rep 10:303. https:\/\/doi.org\/10.1038\/s41598-019-57254-5","journal-title":"Sci Rep"},{"key":"1651_CR4","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s00401-016-1545-1","volume":"131","author":"DN Louis","year":"2016","unstructured":"Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, Ohgaki H, Wiestler OD, Kleihues P, Ellison DW (2016) The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol 131:803\u2013820. https:\/\/doi.org\/10.1007\/s00401-016-1545-1","journal-title":"Acta Neuropathol"},{"key":"1651_CR5","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1016\/S1470-2045(17)30155-9","volume":"18","author":"F Sahm","year":"2017","unstructured":"Sahm F, Schrimpf D, Stichel D, Jones DTW, Hielscher T, Schefzyk S, Okonechnikov K, Koelsche C, Reuss DE, Capper D, Sturm D, Wirsching HG, Berghoff AS, Baumgarten P, Kratz A, Huang K, Wefers AK, Hovestadt V, Sill M, Ellis HP, Kurian KM, Okuducu AF, Jungk C, Drueschler K, Schick M, Bewerunge-Hudler M, Mawrin C, Seiz-Rosenhagen M, Ketter R, Simon M, Westphal M, Lamszus K, Becker A, Koch A, Schittenhelm J, Rushing EJ, Collins VP, Brehmer S, Chavez L, Platten M, Hanggi D, Unterberg A, Paulus W, Wick W, Pfister SM, Mittelbronn M, Preusser M, Herold-Mende C, Weller M, von Deimling A (2017) DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol 18:682\u2013694. https:\/\/doi.org\/10.1016\/S1470-2045(17)30155-9","journal-title":"Lancet Oncol"},{"key":"1651_CR6","doi-asserted-by":"publisher","first-page":"i4","DOI":"10.1093\/neuonc\/noy178","volume":"21","author":"S Suppiah","year":"2019","unstructured":"Suppiah S, Nassiri F, Bi WL, Dunn IF, Hanemann CO, Horbinski CM, Hashizume R, James CD, Mawrin C, Noushmehr H, Perry A, Sahm F, Sloan A, Von Deimling A, Wen PY, Aldape K, Zadeh G, International Consortium on M (2019) Molecular and translational advances in meningiomas. Neuro Oncol 21:i4\u2013i17. https:\/\/doi.org\/10.1093\/neuonc\/noy178","journal-title":"Neuro Oncol"},{"key":"1651_CR7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1089\/cbr.2014.1741","volume":"30","author":"A Dash","year":"2015","unstructured":"Dash A, Chakraborty S, Pillai MR, Knapp FF Jr (2015) Peptide receptor radionuclide therapy: an overview. Cancer Biother Radiopharm 30:47\u201371. https:\/\/doi.org\/10.1089\/cbr.2014.1741","journal-title":"Cancer Biother Radiopharm"},{"issue":"Suppl 1","key":"1651_CR8","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1159\/000080742","volume":"80","author":"JC Reubi","year":"2004","unstructured":"Reubi JC (2004) Somatostatin and other Peptide receptors as tools for tumor diagnosis and treatment. Neuroendocrinology 80(Suppl 1):51\u201356. https:\/\/doi.org\/10.1159\/000080742","journal-title":"Neuroendocrinology"},{"key":"1651_CR9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1089\/cbr.2013.1599","volume":"29","author":"F Minutoli","year":"2014","unstructured":"Minutoli F, Amato E, Sindoni A, Cardile D, Conti A, Herberg A, Baldari S (2014) Peptide receptor radionuclide therapy in patients with inoperable meningiomas: our experience and review of the literature. Cancer Biother Radiopharm 29:193\u2013199. https:\/\/doi.org\/10.1089\/cbr.2013.1599","journal-title":"Cancer Biother Radiopharm"},{"key":"1651_CR10","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1093\/neuonc\/now060","volume":"18","author":"K Seystahl","year":"2016","unstructured":"Seystahl K, Stoecklein V, Schuller U, Rushing E, Nicolas G, Schafer N, Ilhan H, Pangalu A, Weller M, Tonn JC, Sommerauer M, Albert NL (2016) Somatostatin receptor-targeted radionuclide therapy for progressive meningioma: benefit linked to 68Ga-DOTATATE\/-TOC uptake. Neuro Oncol 18:1538\u20131547. https:\/\/doi.org\/10.1093\/neuonc\/now060","journal-title":"Neuro Oncol"},{"key":"1651_CR11","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1023\/b:neon.0000013498.19981.55","volume":"66","author":"S Arena","year":"2004","unstructured":"Arena S, Barbieri F, Thellung S, Pirani P, Corsaro A, Villa V, Dadati P, Dorcaratto A, Lapertosa G, Ravetti JL, Spaziante R, Schettini G, Florio T (2004) Expression of somatostatin receptor mRNA in human meningiomas and their implication in in vitro antiproliferative activity. J Neurooncol 66:155\u2013166. https:\/\/doi.org\/10.1023\/b:neon.0000013498.19981.55","journal-title":"J Neurooncol"},{"key":"1651_CR12","first-page":"485","volume":"20","author":"V Barresi","year":"2008","unstructured":"Barresi V, Alafaci C, Salpietro F, Tuccari G (2008) Sstr2A immunohistochemical expression in human meningiomas: is there a correlation with the histological grade, proliferation or microvessel density? Oncol Rep 20:485\u2013492","journal-title":"Oncol Rep"},{"key":"1651_CR13","first-page":"13185","volume":"8","author":"CB Silva","year":"2015","unstructured":"Silva CB, Ongaratti BR, Trott G, Haag T, Ferreira NP, Leaes CG, Pereira-Lima JF, Oliveira Mda C (2015) Expression of somatostatin receptors (SSTR1-SSTR5) in meningiomas and its clinicopathological significance. Int J Clin Exp Pathol 8:13185\u201313192","journal-title":"Int J Clin Exp Pathol"},{"key":"1651_CR14","doi-asserted-by":"publisher","DOI":"10.1007\/s10143-021-01552-y","author":"F Behling","year":"2021","unstructured":"Behling F, Fodi C, Skardelly M, Renovanz M, Castaneda S, Tabatabai G, Honegger J, Tatagiba M, Schittenhelm J (2021) Differences in the expression of SSTR1-5 in meningiomas and its therapeutic potential. Neurosurg Rev. https:\/\/doi.org\/10.1007\/s10143-021-01552-y","journal-title":"Neurosurg Rev"},{"key":"1651_CR15","doi-asserted-by":"publisher","unstructured":"Sahm F, Schrimpf D, Olar A, Koelsche C, Reuss D, Bissel J, Kratz A, Capper D, Schefzyk S, Hielscher T, Wang Q, Sulman EP, Adeberg S, Koch A, Okuducu AF, Brehmer S, Schittenhelm J, Becker A, Brokinkel B, Schmidt M, Ull T, Gousias K, Kessler AF, Lamszus K, Debus J, Mawrin C, Kim YJ, Simon M, Ketter R, Paulus W, Aldape KD, Herold-Mende C, von Deimling A (2016) TERT promoter mutations and risk of recurrence in meningioma. J Natl Cancer Inst 108. https:\/\/doi.org\/10.1093\/jnci\/djv377","DOI":"10.1093\/jnci\/djv377"},{"key":"1651_CR16","doi-asserted-by":"publisher","first-page":"1278","DOI":"10.1093\/neuonc\/noq081","volume":"12","author":"E Perez-Magan","year":"2010","unstructured":"Perez-Magan E, Rodriguez de Lope A, Ribalta T, Ruano Y, Campos-Martin Y, Perez-Bautista G, Garcia JF, Garcia-Claver A, Fiano C, Hernandez-Moneo JL, Mollejo M, Melendez B (2010) Differential expression profiling analyses identifies downregulation of 1p, 6q, and 14q genes and overexpression of 6p histone cluster 1 genes as markers of recurrence in meningiomas. Neuro Oncol 12:1278\u20131290. https:\/\/doi.org\/10.1093\/neuonc\/noq081","journal-title":"Neuro Oncol"},{"key":"1651_CR17","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1196\/annals.1294.012","volume":"1014","author":"H Lahlou","year":"2004","unstructured":"Lahlou H, Guillermet J, Hortala M, Vernejoul F, Pyronnet S, Bousquet C, Susini C (2004) Molecular signaling of somatostatin receptors. Ann N Y Acad Sci 1014:121\u2013131. https:\/\/doi.org\/10.1196\/annals.1294.012","journal-title":"Ann N Y Acad Sci"},{"key":"1651_CR18","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1006\/bbrc.1994.1088","volume":"198","author":"YC Patel","year":"1994","unstructured":"Patel YC, Greenwood MT, Warszynska A, Panetta R, Srikant CB (1994) All five cloned human somatostatin receptors (hSSTR1-5) are functionally coupled to adenylyl cyclase. Biochem Biophys Res Commun 198:605\u2013612. https:\/\/doi.org\/10.1006\/bbrc.1994.1088","journal-title":"Biochem Biophys Res Commun"},{"key":"1651_CR19","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/s0165-6147(00)88992-0","volume":"16","author":"JC Reubi","year":"1995","unstructured":"Reubi JC, Laissue JA (1995) Multiple actions of somatostatin in neoplastic disease. Trends Pharmacol Sci 16:110\u2013115. https:\/\/doi.org\/10.1016\/s0165-6147(00)88992-0","journal-title":"Trends Pharmacol Sci"},{"key":"1651_CR20","doi-asserted-by":"publisher","first-page":"1733","DOI":"10.1093\/annonc\/mdl105","volume":"17","author":"C Susini","year":"2006","unstructured":"Susini C, Buscail L (2006) Rationale for the use of somatostatin analogs as antitumor agents. Ann Oncol 17:1733\u20131742. https:\/\/doi.org\/10.1093\/annonc\/mdl105","journal-title":"Ann Oncol"},{"key":"1651_CR21","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1007\/BF00294492","volume":"20","author":"B Szende","year":"1992","unstructured":"Szende B, Juhasz E, Lapis K, Schally AV (1992) Inhibition of two-step urinary bladder carcinogenesis by the somatostatin analogue RC-160. Urol Res 20:383\u2013386. https:\/\/doi.org\/10.1007\/BF00294492","journal-title":"Urol Res"},{"key":"1651_CR22","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1210\/jcem.74.3.1346787","volume":"74","author":"JW Koper","year":"1992","unstructured":"Koper JW, Markstein R, Kohler C, Kwekkeboom DJ, Avezaat CJ, Lamberts SW, Reubi JC (1992) Somatostatin inhibits the activity of adenylate cyclase in cultured human meningioma cells and stimulates their growth. J Clin Endocrinol Metab 74:543\u2013547. https:\/\/doi.org\/10.1210\/jcem.74.3.1346787","journal-title":"J Clin Endocrinol Metab"}],"updated-by":[{"DOI":"10.1007\/s10143-022-01817-0","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,5,23]],"date-time":"2022-05-23T00:00:00Z","timestamp":1653264000000}}],"container-title":["Neurosurgical Review"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10143-021-01651-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10143-021-01651-w\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10143-021-01651-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,3]],"date-time":"2022-08-03T09:04:09Z","timestamp":1659517449000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10143-021-01651-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,2]]},"references-count":22,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["1651"],"URL":"https:\/\/doi.org\/10.1007\/s10143-021-01651-w","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s10143-022-01817-0","asserted-by":"object"}]},"ISSN":["1437-2320"],"issn-type":[{"value":"1437-2320","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,2]]},"assertion":[{"value":"7 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 September 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 September 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 October 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 May 2022","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s10143-022-01817-0","URL":"https:\/\/doi.org\/10.1007\/s10143-022-01817-0","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Clinical Ethics Committee of the University of T\u00fcbingen (Project number: 618\/2014BO2).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Tumor tissue and clinical data were only used if patient consent was available as defined by the Clinical Ethics Committee of the University of T\u00fcbingen.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}