Do Hwan Kim , Saima Siddiqui , Preetesh Jain , Michael Wang , Beenu Thakral , Shaoying Li , Roberto Miranda , Francisco Vega , L. Jeffrey Medeiros , Chi Young Ok
{"title":"TP53 mutation is frequent in mantle cell lymphoma with EZH2 expression and have dismal outcome when both are present","authors":"Do Hwan Kim , Saima Siddiqui , Preetesh Jain , Michael Wang , Beenu Thakral , Shaoying Li , Roberto Miranda , Francisco Vega , L. Jeffrey Medeiros , Chi Young Ok","doi":"10.1016/j.humpath.2024.03.002","DOIUrl":null,"url":null,"abstract":"<div><p>Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (<em>ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2</em> and <em>UBR5</em>) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor <em>TP53</em> mutation compared to EZH2(−) MCL (41.2% vs. 19.1%, respectively, p = 0.045). <em>TP53</em> mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of <em>TP53</em> mutation. Aggressive histology is associated with EZH2 expression or <em>TP53</em> mutation, possibly via independent mechanisms. p53 mutant pattern is due to <em>TP53</em> mutation. MCL patients with EZH2 expression or <em>TP53</em> mutation show inferior outcome and when both are present, patients have dismal outcome.</p></div>","PeriodicalId":13062,"journal":{"name":"Human pathology","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0046817724000388/pdfft?md5=f1dcdf115fabe5efc0da99628259762b&pid=1-s2.0-S0046817724000388-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Human pathology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0046817724000388","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PATHOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Enhancer of zeste homolog 2 (EZH2) expression is found in about 40% of mantle cell lymphoma (MCL) patients, which is associated with aggressive histology, high Ki-67 proliferation rate, p53 mutant pattern and inferior overall survival (OS). We conducted 11-gene (ATM, BIRC3, CCND1, KMT2C, KMT2D, NOTCH1, NOTCH2, RB1, TP53, TRAF2 and UBR5) next generation sequencing panel to shed more light on MCL with EZH2 expression (EZH2+ MCL). EZH2+ MCL more frequently harbor TP53 mutation compared to EZH2(−) MCL (41.2% vs. 19.1%, respectively, p = 0.045). TP53 mutation and EZH2 expression demonstrated overlapping features including aggressive histology, high Ki-67 proliferation rate and p53 mutant pattern by immunohistochemistry. Comparative analysis disclosed that EZH2 expression correlates with high Ki-67 proliferation rate irrespective of TP53 mutation. Aggressive histology is associated with EZH2 expression or TP53 mutation, possibly via independent mechanisms. p53 mutant pattern is due to TP53 mutation. MCL patients with EZH2 expression or TP53 mutation show inferior outcome and when both are present, patients have dismal outcome.
期刊介绍:
Human Pathology is designed to bring information of clinicopathologic significance to human disease to the laboratory and clinical physician. It presents information drawn from morphologic and clinical laboratory studies with direct relevance to the understanding of human diseases. Papers published concern morphologic and clinicopathologic observations, reviews of diseases, analyses of problems in pathology, significant collections of case material and advances in concepts or techniques of value in the analysis and diagnosis of disease. Theoretical and experimental pathology and molecular biology pertinent to human disease are included. This critical journal is well illustrated with exceptional reproductions of photomicrographs and microscopic anatomy.