{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T03:12:29Z","timestamp":1781665949789,"version":"3.54.5"},"reference-count":27,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea","award":["NRF- 2022R1I1A1A01071569"],"award-info":[{"award-number":["NRF- 2022R1I1A1A01071569"]}]},{"name":"St. Vincent\u2019s hospital, research institute of medical science","award":["SVHR-2022-05"],"award-info":[{"award-number":["SVHR-2022-05"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Exp Med"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Friend Leukemia Virus Integration 1 (FLI-1) is a member of E26 transformation-specific family of transcription factors that participates in hematopoietic and vascular endothelial cell development. Immunohistochemical detection of FLI-1 has been widely used to diagnose vascular tumors or, more evidently, Ewing\u2019s sarcoma. However, the expression pattern of FLI-1 in hematolymphoid neoplasms remains unclear. Therefore, in this study, we aimed to investigate the expression of FLI-1 in these tumors, focusing on high-grade lesions, which presents a diagnostic challenge by mimicking Ewing\u2019s sarcoma. We evaluated the expression FLI-1 in various types of lymphoid and plasmacytic tumors, including 27 plasmablastic lymphomas, 229 diffuse large B-cell lymphomas, 22 precursor T- or B-lymphoblastic lymphomas, 24 angioimmunoblastic-type nodal T-follicular helper cell lymphomas, 52 peripheral T-cell lymphomas, NOS, 18 Burkitt lymphomas, 18 non-gastric lymphomas of mucosa-associated lymphoid tissue, 38 chronic lymphocytic leukemia\/small lymphocytic lymphomas, 15 mantle cell lymphomas, 23 gastric MALT lymphomas, 50 plasma cell myelomas, and 38 follicular lymphomas. We calculated the H-scores of FLI-1 immunostaining, ranging from 0 to 200, and used the scores to analyze the clinicopathological significance of FLI-1 statistically. FLI-1 was expressed to varying degrees in all types of hematological tumors. FLI-1 expression was detected in 84.1% of patients (466\/554). FLI-1 was highly expressed in precursor T- or B-lymphoblastic lymphomas. Follicular lymphomas exhibited low FLI-1 expression. In plasmablastic lymphoma, 85.2% of the patients were focally positive for FLI-1. FLI-1 expression did not correlate with clinicopathological variables, such as demographic data or disease stage, in patients with plasmablastic lymphoma and diffuse large B-cell lymphoma. However, FLI-1 overexpression was associated with poorer overall survival in patients with plasmablastic lymphoma. This study demonstrates that FLI-1 is expressed in various hematolymphoid neoplasms. FLI-1 expression can lead to diagnostic confusion, especially in small blue round cell tumors, such as lymphoblastic lymphoma, plasmablastic lymphoma, and plasma cell myeloma, when distinguishing tumors positive for CD99 and CD56 without CD3, CD20, or CD45. Our findings also suggested the possibility of FLI-1 as a potential prognostic biomarker for plasmablastic lymphoma.<\/jats:p>","DOI":"10.1007\/s10238-023-01284-x","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T11:02:21Z","timestamp":1706353341000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["FLI-1 is expressed in a wide variety of hematolymphoid neoplasms: a special concern in the differential diagnosis"],"prefix":"10.1007","volume":"24","author":[{"given":"Uiju","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Jeong","family":"Cha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyun Jung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Kee","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee Kyung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Ra","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyeongsin","family":"Park","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Eun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,1,27]]},"reference":[{"key":"1284_CR1","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/s00005-006-0017-z","volume":"54","author":"S Gallant","year":"2006","unstructured":"Gallant S, Gilkeson G. ETS transcription factors and regulation of immunity. Arch Immunol Ther Exp (Warsz). 2006;54:149\u201363. https:\/\/doi.org\/10.1007\/s00005-006-0017-z.","journal-title":"Arch Immunol Ther Exp (Warsz)"},{"key":"1284_CR2","doi-asserted-by":"publisher","first-page":"4449","DOI":"10.1128\/mcb.12.10.4449-4455.1992","volume":"12","author":"Y Ben-David","year":"1992","unstructured":"Ben-David Y, Bani MR, Chabot B, De Koven A, Bernstein A. Retroviral insertions downstream of the heterogeneous nuclear ribonucleoprotein A1 gene in erythroleukemia cells: evidence that A1 is not essential for cell growth. Mol Cell Biol. 1992;12:4449\u201355. https:\/\/doi.org\/10.1128\/mcb.12.10.4449-4455.1992.","journal-title":"Mol Cell Biol"},{"key":"1284_CR3","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1101\/gad.5.6.908","volume":"5","author":"Y Ben-David","year":"1991","unstructured":"Ben-David Y, Giddens EB, Letwin K, Bernstein A. Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev. 1991;5:908\u201318. https:\/\/doi.org\/10.1101\/gad.5.6.908.","journal-title":"Genes Dev"},{"key":"1284_CR4","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/359162a0","volume":"359","author":"O Delattre","year":"1992","unstructured":"Delattre O, Zucman J, Plougastel B, Desmaze C, Melot T, Peter M, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumors. Nature. 1992;359:162\u20135. https:\/\/doi.org\/10.1038\/359162a0.","journal-title":"Nature"},{"key":"1284_CR5","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1097\/00000478-200012000-00010","volume":"24","author":"AL Folpe","year":"2000","unstructured":"Folpe AL, Hill CE, Parham DM, O\u2019Shea PA, Weiss SW. Immunohistochemical detection of FLI-1 protein expression: a study of 132 round cell tumors with emphasis on CD99-positive mimics of Ewing\u2019s sarcoma\/primitive neuroectodermal tumor. Am J Surg Pathol. 2000;24:1657\u201362. https:\/\/doi.org\/10.1097\/00000478-200012000-00010.","journal-title":"Am J Surg Pathol"},{"key":"1284_CR6","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1097\/00000478-200108000-00011","volume":"25","author":"AL Folpe","year":"2001","unstructured":"Folpe AL, Chand EM, Goldblum JR, Weiss SW. Expression of Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol. 2001;25:1061\u20136. https:\/\/doi.org\/10.1097\/00000478-200108000-00011.","journal-title":"Am J Surg Pathol"},{"key":"1284_CR7","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1080\/13577149977839","volume":"3","author":"G Nilsson","year":"1999","unstructured":"Nilsson G, Wang M, Wejde J, Kreicbergs A, Larsson O. Detection of EWS\/FLI-1 by immunostaining. An adjunctive tool in diagnosis of Ewing\u2019s sarcoma and primitive neuroectodermal tumour on cytological samples and paraffin-embedded archival material. Sarcoma. 1999;3:25\u201332. https:\/\/doi.org\/10.1080\/13577149977839.","journal-title":"Sarcoma"},{"key":"1284_CR8","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1097\/00129039-200109000-00010","volume":"9","author":"A Llombart-Bosch","year":"2001","unstructured":"Llombart-Bosch A, Navarro S. Immunohistochemical detection of EWS and FLI-1 proteinss in Ewing sarcoma and primitive neuroectodermal tumors: comparative analysis with CD99 (MIC-2) expression. Appl Immunohistochem Mol Morphol. 2001;9:255\u201360. https:\/\/doi.org\/10.1097\/00129039-200109000-00010.","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"1284_CR9","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1097\/PAI.0b013e3181972b6d","volume":"17","author":"O Lin","year":"2009","unstructured":"Lin O, Filippa DA, Teruya-Feldstein J. Immunohistochemical evaluation of FLI-1 in acute lymphoblastic lymphoma (ALL): a potential diagnostic pitfall. Appl Immunohistochem Mol Morphol. 2009;17:409\u201312. https:\/\/doi.org\/10.1097\/PAI.0b013e3181972b6d.","journal-title":"Appl Immunohistochem Mol Morphol"},{"key":"1284_CR10","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1136\/jcp.2006.039230","volume":"60","author":"P Mhawech-Fauceglia","year":"2007","unstructured":"Mhawech-Fauceglia P, Herrmann FR, Bshara W, Odunsi K, Terracciano L, Sauter G, et al. Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody. J Clin Pathol. 2007;60:694\u2013700. https:\/\/doi.org\/10.1136\/jcp.2006.039230.","journal-title":"J Clin Pathol"},{"key":"1284_CR11","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","volume":"36","author":"R Alaggio","year":"2022","unstructured":"Alaggio R, Amador C, Anagnostopoulos I, Attygalle AD, Araujo IBO, Berti E, et al. The 5th edition of the World Health Organization classification of hematolymphoid tumors: lymphoid neoplasms. Leukemia. 2022;36:1720\u201348. https:\/\/doi.org\/10.1038\/s41375-022-01620-2.","journal-title":"Leukemia"},{"key":"1284_CR12","doi-asserted-by":"publisher","first-page":"2022","DOI":"10.1038\/onc.2014.162","volume":"34","author":"Y Li","year":"2015","unstructured":"Li Y, Luo H, Liu T, Zacksenhaus E, Ben-David Y. The ets transcription factor Fli-1 in development, cancer, and disease. Oncogene. 2015;34:2022\u201331. https:\/\/doi.org\/10.1038\/onc.2014.162.","journal-title":"Oncogene"},{"key":"1284_CR13","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1309\/K1XJ-6CXR-BQQU-V255","volume":"115","author":"DR Lucas","year":"2001","unstructured":"Lucas DR, Bentley G, Dan ME, Tabaczka P, Poulik JM, Mott MP. Ewing sarcoma vs lymphoblastic lymphoma. A comparative immunohistochemical study. Am J Clin Pathol. 2001;115:11\u20137. https:\/\/doi.org\/10.1309\/K1XJ-6CXR-BQQU-V255.","journal-title":"Am J Clin Pathol"},{"key":"1284_CR14","doi-asserted-by":"publisher","first-page":"456","DOI":"10.3892\/ijo.2017.4027","volume":"51","author":"LM Vecchiarelli-Federico","year":"2017","unstructured":"Vecchiarelli-Federico LM, Liu T, Yao Y, Gao Y, Li Y, Li YJ, et al. Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1\/PU.1 exerts the opposite effect. Int J Oncol. 2017;51:456\u201366. https:\/\/doi.org\/10.3892\/ijo.2017.4027.","journal-title":"Int J Oncol"},{"key":"1284_CR15","doi-asserted-by":"publisher","first-page":"3548","DOI":"10.1002\/cam4.1589","volume":"7","author":"X Yan","year":"2018","unstructured":"Yan X, Yu Y, Li L, Chen N, Song W, He H, et al. Friend leukemia virus integration 1 is a predictor of poor prognosis of breast cancer and promotes metastasis and cancer stem cell properties of breast cancer cells. Cancer Med. 2018;7:3548\u201360. https:\/\/doi.org\/10.1002\/cam4.1589.","journal-title":"Cancer Med"},{"key":"1284_CR16","doi-asserted-by":"publisher","first-page":"5604","DOI":"10.1182\/blood-2011-04-348052","volume":"118","author":"SM Kornblau","year":"2011","unstructured":"Kornblau SM, Qiu YH, Zhang N, Singh N, Faderl S, Ferrajoli A, et al. Abnormal expression of FLI1 protein is an adverse prognostic factor in acute myeloid leukemia. Blood. 2011;118:5604\u201312. https:\/\/doi.org\/10.1182\/blood-2011-04-348052.","journal-title":"Blood"},{"key":"1284_CR17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0062346","volume":"8","author":"MFMA Smeets","year":"2013","unstructured":"Smeets MFMA, Chan AC, Dagger S, Bradley CK, Wei A, Izon DJ. Fli-1 overexpression in hematopoietic progenitors deregulates T cell development and induces pre-T cell lymphoblastic leukaemia\/lymphoma. PLoS ONE. 2013;8: e62346. https:\/\/doi.org\/10.1371\/journal.pone.0062346.","journal-title":"PLoS ONE"},{"key":"1284_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.biochi.2019.10.005","volume":"168","author":"SW Park","year":"2020","unstructured":"Park SW, Do HJ, Choi W, Kim JH. Fli-1 promotes proliferation and upregulates NANOGP8 expression in T-lymphocyte leukemia cells. Biochimie. 2020;168:1\u20139. https:\/\/doi.org\/10.1016\/j.biochi.2019.10.005.","journal-title":"Biochimie"},{"key":"1284_CR19","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1186\/1471-2407-14-424","volume":"14","author":"W Song","year":"2014","unstructured":"Song W, Hu L, Li W, Wang G, Li Y, Yan L, et al. Oncogenic Fli-1 is a potential prognostic marker for the progression of epithelial ovarian cancer. BMC Cancer. 2014;14:424. https:\/\/doi.org\/10.1186\/1471-2407-14-424.","journal-title":"BMC Cancer"},{"key":"1284_CR20","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1002\/ijc.32831","volume":"147","author":"B Miao","year":"2020","unstructured":"Miao B, Bauer AS, Hufnagel K, Wu Y, Trajkovic-Arsic M, Pirona AC, et al. The transcription factor FLI1 promotes cancer progression by affecting cell cycle regulation. Int J Cancer. 2020;147:189\u2013201. https:\/\/doi.org\/10.1002\/ijc.32831.","journal-title":"Int J Cancer"},{"key":"1284_CR21","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1016\/j.ijbiomac.2022.04.076","volume":"209","author":"L Li","year":"2022","unstructured":"Li L, Yu J, Cheng S, Peng Z, Luo H. Transcription factor Fli-1 as a new target for antitumor drug development. Int J Biol Macromol. 2022;209:1155\u201368. https:\/\/doi.org\/10.1016\/j.ijbiomac.2022.04.076.","journal-title":"Int J Biol Macromol"},{"key":"1284_CR22","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/s0378-1119(02)01156-3","volume":"303","author":"T Oikawa","year":"2003","unstructured":"Oikawa T, Yamada T. Molecular biology of the ets family of transcription factors. Gene. 2003;303:11\u201334. https:\/\/doi.org\/10.1016\/s0378-1119(02)01156-3.","journal-title":"Gene"},{"key":"1284_CR23","doi-asserted-by":"publisher","first-page":"6432","DOI":"10.1038\/sj.onc.1204039","volume":"19","author":"IG Maroulakou","year":"2000","unstructured":"Maroulakou IG, Bowe DB. Expression and function of ets transcription factors in mammalian development: a regulatory network. Oncogene. 2000;19:6432\u201342. https:\/\/doi.org\/10.1038\/sj.onc.1204039.","journal-title":"Oncogene"},{"key":"1284_CR24","first-page":"551","volume":"7","author":"B Davidson","year":"2001","unstructured":"Davidson B, Reich R, Goldberg I, Gotlieb WH, Kopolovic J, Berner A, et al. Ets-1 messenger RNA expression is a novel marker of poor survival in ovarian carcinoma. Clin Cancer Res. 2001;7:551\u20137.","journal-title":"Clin Cancer Res"},{"key":"1284_CR25","doi-asserted-by":"publisher","first-page":"5507","DOI":"10.1038\/sj.onc.1203946","volume":"19","author":"G Foos","year":"2000","unstructured":"Foos G, Hauser CA. Altered ets transcription factor activity in prostate tumor cells inhibits anchorage-independent growth, survival, and invasiveness. Oncogene. 2000;19:5507\u201316. https:\/\/doi.org\/10.1038\/sj.onc.1203946.","journal-title":"Oncogene"},{"key":"1284_CR26","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.neo.2014.08.007","volume":"16","author":"MN Scheiber","year":"2014","unstructured":"Scheiber MN, Watson PM, Rumboldt T, Stanley C, Wilson RC, Findlay VJ, et al. FLI1 expression is correlated with breast cancer cellular growth, migration, and invasion and altered gene expression. Neoplasia. 2014;16:801\u201313. https:\/\/doi.org\/10.1016\/j.neo.2014.08.007.","journal-title":"Neoplasia"},{"key":"1284_CR27","doi-asserted-by":"publisher","first-page":"469","DOI":"10.3109\/07357907.2015.1069831","volume":"33","author":"W Song","year":"2015","unstructured":"Song W, Zhang T, Li W, Mu R, Zhang L, Li Y, et al. Overexpression of Fli-1 is associated with adverse prognosis of endometrial cancer. Cancer Invest. 2015;33:469\u201375. https:\/\/doi.org\/10.3109\/07357907.2015.1069831.","journal-title":"Cancer Invest"}],"container-title":["Clinical and Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-023-01284-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10238-023-01284-x\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10238-023-01284-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,30]],"date-time":"2024-11-30T17:07:49Z","timestamp":1732986469000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10238-023-01284-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,27]]},"references-count":27,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1284"],"URL":"https:\/\/doi.org\/10.1007\/s10238-023-01284-x","relation":{},"ISSN":["1591-9528"],"issn-type":[{"value":"1591-9528","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,27]]},"assertion":[{"value":"19 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 January 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All authors read and approved the final manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The dataset supporting the conclusions of this article is included within the report.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Availability of data and materials"}}],"article-number":"18"}}