{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T21:31:52Z","timestamp":1740173512868,"version":"3.37.3"},"reference-count":29,"publisher":"Endocrinology Research Centre","issue":"6","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.probl-endojournals.ru\/jour\/about\/editorialPolicies#openAccessPolicy"}],"content-domain":{"domain":["www.probl-endojournals.ru"],"crossmark-restriction":true},"short-container-title":["Probl Endokrinol (Mosk)"],"abstract":"<jats:p><jats:bold>BACKGROUND<\/jats:bold>: Multiple endocrine neoplasia type 1 (MEN\u00a01) is a rare autosomal dominant disorder caused by mutations in the MEN1 gene, which encodes the menin protein. If a patient has the MEN\u00a01 phenotype in the absence of mutations in\u00a0the\u00a0MEN1 gene, the condition is classified as a phenocopy of this syndrome. Although significant progress has been made in understanding the function of menin, its role in the oncogenesis of the endocrine glands is still being elucidated. Due to its key role in physiological and pathological processes, the assessment of the menin expression can provide valuable information.<\/jats:p><jats:p><jats:bold>AIM<\/jats:bold>: to determine whether there are any differences in the expression of menin in the pituitary adenomas (PA) in patients with phenocopy of MEN\u00a01 (phMEN\u00a01) and genetically confirmed MEN\u00a01 (gMEN\u00a01) compared with their sporadic forms.<\/jats:p><jats:p><jats:bold>MATERIALS AND METHODS<\/jats:bold>: immunohistochemical assessment of the menin expression was carried out in PA of patients with gMEN\u00a01, phMEN\u00a01 and sporadic acromegaly (SA), surgically treated in 2008\u20132020. IHC was performed using antibodies to menin, PRL, GH, ACTH, FSH, TSH, Pit-1, T-box, ERA on previously prepared histological section.<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold>: The study included 35 samples of PA: gMEN\u00a01 \u2014 9 samples, phMEN\u00a01 \u2014 12 (somatotropinomas + PHPT); CA \u2014 14\u00a0 samples. The patients were comparable by gender, adenoma size, and drug intake. The gMEN\u00a0 1 group differed from phMEN\u00a01 and SA by age (p = 0.0005). In patients with gMEN\u00a01, the expression of menin varied from no staining (5\/9) to intense cytoplasm staining. Cytoplasmic expression of menin was mainly present (11\/12) in the phMEN\u00a01. In the SA group, there was no staining in 1 case; nuclear expression was detected in 6\/14 cases. The phMEN\u00a0 1 group showed significantly higher cytoplasmic expression of menin than the gMEN\u00a0 1 group (p = 0.006). The\u00a0gMEN\u00a01 group also differed from the SA group (p = 0.012). There were no statistically significant differences between the\u00a0phMEN\u00a01 and SA groups (p = 0.049).<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold>: It was revealed that the menin expression, in general, is retained in phMEN\u00a01 and SA groups, although with different localization in the cell structure (nucleus and \/ or cytoplasm). At the same time, the expression of menin varies greatly in patients with gMEN\u00a01. According to the data obtained, it can be assumed that the pathogenesis of PA in\u00a0phMEN\u00a01 and SA may have similarities; however, there could be factors contributing to the appearance of several tumors of the endocrine glands in one person with phMEN\u00a01. To understand this process, it is necessary to further study the genes associated with MEN\u00a01, epigenetic factors, signaling pathways in which menin is involved.<\/jats:p>","DOI":"10.14341\/probl12815","type":"journal-article","created":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T09:11:47Z","timestamp":1641978707000},"page":"50-58","update-policy":"https:\/\/doi.org\/10.14341\/crossmarkpolicy2018","source":"Crossref","is-referenced-by-count":1,"title":["Morphological characteristics of pituitary adenomas in the phenocopy of multiple endocrine neoplasia type 1"],"prefix":"10.14341","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1359-8297","authenticated-orcid":true,"given":"D. A.","family":"Trukhina","sequence":"first","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9783-3599","authenticated-orcid":true,"given":"E. O.","family":"Mamedova","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4353-6705","authenticated-orcid":true,"given":"A. M.","family":"Lapshina","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3780-3758","authenticated-orcid":true,"given":"E. V.","family":"Vasilyev","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8500-4841","authenticated-orcid":true,"given":"A. N.","family":"Tiulpakov","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre;\r\nResearch Centre for Medical Genetics"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6674-6441","authenticated-orcid":true,"given":"Zh. E.","family":"Belaya","sequence":"additional","affiliation":[{"name":"Endocrinology Research Centre"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"5458","published-online":{"date-parts":[[2021,10,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Lim CT, Korbonits M. UPDATE ON THE CLINICOPATHOLOGY OF PITUITARY ADENOMAS. Endocr Pract. 2018;24(5):473-488. doi:10.4158\/EP-2018-0034","DOI":"10.4158\/EP-2018-0034"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Daly AF, Rixhon M, Adam C, Dempegioti A, Tichomirowa MA, Beckers A. High prevalence of pituitary adenomas: a cross-sectional study in the province of Liege, Belgium. J Clin Endocrinol Metab. 2006;91(12):4769-4775. doi:10.1210\/jc.2006-1668","DOI":"10.1210\/jc.2006-1668"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Tatsi C, Stratakis CA. The Genetics of Pituitary Adenomas. J Clin Med. 2019;9(1):30. Published 2019 Dec 21. doi:10.3390\/jcm9010030","DOI":"10.3390\/jcm9010030"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Giusti F, Cianferotti L, Boaretto F, et al. Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database. Endocrine. 2017;58(2):349-359. doi:10.1007\/s12020-017-1234-4","DOI":"10.1007\/s12020-017-1234-4"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"de Laat JM, Dekkers OM, Pieterman CR, et al. Long-Term Natural Course of Pituitary Tumors in Patients With MEN1: Results From the DutchMEN1 Study Group (DMSG). J Clin Endocrinol Metab. 2015;100(9):3288-3296. doi:10.1210\/JC.2015-2015","DOI":"10.1210\/JC.2015-2015"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Karhu A, Aaltonen LA. Susceptibility to pituitary neoplasia related to MEN-1, CDKN1B and AIP mutations: an update. Hum Mol Genet. 2007;16 Spec No 1:R73-R79. doi:10.1093\/hmg\/ddm036","DOI":"10.1093\/hmg\/ddm036"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Falchetti A. Genetics of multiple endocrine neoplasia type 1 syndrome: what's new and what's old. F1000Res. 2017;6:F1000 Faculty Rev-73. Published 2017 Jan 24. doi:10.12688\/f1000research.7230.1","DOI":"10.12688\/f1000research.7230.1"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Thakker RV, Newey PJ, Walls GV, et al. Clinical practice guidelines for multiple endocrine neoplasia type 1 (MEN1). J Clin Endocrinol Metab. 2012;97(9):2990-3011. doi:10.1210\/jc.2012-1230","DOI":"10.1210\/jc.2012-1230"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Nachtigall LB, Guarda FJ, Lines KE, et al. Clinical MEN-1 Among a Large Cohort of Patients With Acromegaly. J Clin Endocrinol Metab. 2020;105(6):e2271-e2281. doi:10.1210\/clinem\/dgaa142","DOI":"10.1210\/clinem\/dgaa142"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskj\u00f6ld M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature. 1988;332(6159):85-87. doi:10.1038\/332085a0","DOI":"10.1038\/332085a0"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Matkar S, Thiel A, Hua X. Menin: a scaffold protein that controls gene expression and cell signaling. Trends Biochem Sci. 2013;38(8):394-402. doi:10.1016\/j.tibs.2013.05.005","DOI":"10.1016\/j.tibs.2013.05.005"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Kaji H, Canaff L, Lebrun JJ, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling. Proc Natl Acad Sci U S A. 2001;98(7):3837-3842. doi:10.1073\/pnas.061358098","DOI":"10.1073\/pnas.061358098"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Franklin DS, Godfrey VL, O'Brien DA, Deng C, Xiong Y. Functional collaboration between different cyclin-dependent kinase inhibitors suppresses tumor growth with distinct tissue specificity. Mol Cell Biol. 2000;20(16):6147-6158. doi:10.1128\/MCB.20.16.6147-6158.2000","DOI":"10.1128\/MCB.20.16.6147-6158.2000"},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"Schnepp RW, Chen YX, Wang H, et al. Mutation of tumor suppressor gene Men1 acutely enhances proliferation of pancreatic islet cells. Cancer Res. 2006;66(11):5707-5715. doi:10.1158\/0008-5472.CAN-05-4518","DOI":"10.1158\/0008-5472.CAN-05-4518"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Wrocklage C, Gold H, Hackl W, Buchfelder M, Fahlbusch R, Paulus W. Increased menin expression in sporadic pituitary adenomas. Clin Endocrinol (Oxf). 2002;56(5):589-594. doi:10.1046\/j.1365-2265.2002.01516.x","DOI":"10.1046\/j.1365-2265.2002.01516.x"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Theodoropoulou M, Cavallari I, Barzon L, et al. Differential expression of menin in sporadic pituitary adenomas. Endocr Relat Cancer. 2004;11(2):333-344. doi:10.1677\/erc.0.0110333","DOI":"10.1677\/erc.0.0110333"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Kooblall KG, Boon H, Cranston T, et al. Multiple Endocrine Neoplasia Type 1 (MEN1) 5'UTR Deletion, in MEN1 Family, Decreases Menin Expression. J Bone Miner Res. 2021;36(1):100-109. doi:10.1002\/jbmr.4156","DOI":"10.1002\/jbmr.4156"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424. doi:10.1038\/gim.2015.30","DOI":"10.1038\/gim.2015.30"},{"key":"ref19","doi-asserted-by":"crossref","unstructured":"Ryzhkova OP, Kardymon OL, Prohorchuk EB, et al. Guidelines for the interpretation of massive parallel sequencing variants (update 2018, v2). Medical genetics. 2019;18(2):3\u201324. (In Russ.) doi: 10.25557\/2073-7998.2019.02.3-23","DOI":"10.25557\/2073-7998.2019.02.3-23"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Sonoda A, Yamashita YI, Kondo T, et al. Clinicopathological features and menin expression of pancreatic neuroendocrine neoplasm associated with multiple endocrine neoplasia type 1. J Hepatobiliary Pancreat Sci. 2020;27(12):984-991. doi:10.1002\/jhbp.739","DOI":"10.1002\/jhbp.739"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Corbo V, Dalai I, Scardoni M, et al. MEN1 in pancreatic endocrine tumors: analysis of gene and protein status in 169 sporadic neoplasms reveals alterations in the vast majority of cases. Endocr Relat Cancer. 2010;17(3):771-783. Published 2010 Aug 16. doi:10.1677\/ERC-10-0028","DOI":"10.1677\/ERC-10-0028"},{"key":"ref22","doi-asserted-by":"crossref","unstructured":"Cao Y, Liu R, Jiang X, et al. Nuclear-cytoplasmic shuttling of menin regulates nuclear translocation of {beta}-catenin. Mol Cell Biol. 2009;29(20):5477-5487. doi:10.1128\/MCB.00335-09","DOI":"10.1128\/MCB.00335-09"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Kim B, Song TY, Jung KY, Kim SG, Cho EJ. Direct interaction of menin leads to ubiquitin-proteasomal degradation of \u03b2-catenin. Biochem Biophys Res Commun. 2017;492(1):128-134. doi:10.1016\/j.bbrc.2017.08.011","DOI":"10.1016\/j.bbrc.2017.08.011"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Mensah-Osman E, Zavros Y, Merchant JL. Somatostatin stimulates menin gene expression by inhibiting protein kinase A. Am J Physiol Gastrointest Liver Physiol. 2008;295(4):G843-G854. doi:10.1152\/ajpgi.00607.2007","DOI":"10.1152\/ajpgi.00607.2007"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Zhang H, Li W, Wang Q, et al. Glucose-mediated repression of menin promotes pancreatic \u03b2-cell proliferation. Endocrinology. 2012;153(2):602-611. doi:10.1210\/en.2011-1460","DOI":"10.1210\/en.2011-1460"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"Wu Y, Feng ZJ, Gao SB, et al. Interplay between menin and K-Ras in regulating lung adenocarcinoma. J Biol Chem. 2012;287(47):40003-40011. doi:10.1074\/jbc.M112.382416","DOI":"10.1074\/jbc.M112.382416"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Mamedova EO, Dimitrova DA, Belaya ZhE, et al. The role of non-coding RNAs in the pathogenesis of multiple endocrine neoplasia syndrome type 1. Problems of Endocrinology. 2020;66(2):4\u201312. (In Russ.). doi: 10.14341\/probl12413","DOI":"10.14341\/probl12413"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Luzi E, Marini F, Giusti F, Galli G, Cavalli L, Brandi ML. The negative feedback-loop between the oncomir Mir-24-1 and menin modulates the Men1 tumorigenesis by mimicking the \"Knudson's second hit\". PLoS One. 2012;7(6):e39767. doi:10.1371\/journal.pone.0039767","DOI":"10.1371\/journal.pone.0039767"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Lines KE, Javid M, Reed AAC, et al. Genetic background influences tumour development in heterozygous Men1 knockout mice. Endocr Connect. 2020;9(5):426-437. doi:10.1530\/EC-20-0103","DOI":"10.1530\/EC-20-0103"}],"container-title":["Problems of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/viewFile\/12815\/10015","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2022,1,12]],"date-time":"2022-01-12T09:12:22Z","timestamp":1641978742000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.probl-endojournals.ru\/jour\/article\/view\/12815"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,25]]},"references-count":29,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,1,7]]}},"URL":"https:\/\/doi.org\/10.14341\/probl12815","relation":{},"ISSN":["2308-1430","0375-9660"],"issn-type":[{"type":"electronic","value":"2308-1430"},{"type":"print","value":"0375-9660"}],"subject":[],"published":{"date-parts":[[2021,10,25]]}}}