{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T23:10:26Z","timestamp":1759533026225,"version":"build-2065373602"},"reference-count":38,"publisher":"Georg Thieme Verlag KG","issue":"04","license":[{"start":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T00:00:00Z","timestamp":1746057600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Dent"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Yes-associated protein (YAP) and Ki-67 are known to be involved in cell proliferation. While their overexpression is associated with aggressive behaviors in oral squamous cell carcinoma (OSCC), their roles in odontogenic cysts have not been thoroughly investigated. Therefore, this study aimed to evaluate the immunohistochemical expression of YAP and Ki-67 in odontogenic cysts.<\/jats:p><jats:p>Tissue samples included 12 radicular cysts, 10 dentigerous cysts, 9 odontogenic keratocysts, and 9 normal oral mucosa specimens. Immunohistochemical analysis was conducted both manually and using ImageJ software for comparison.<\/jats:p><jats:p>The Kruskal\u2013Wallis, followed by the Mann\u2013Whitney U-test was used to assess the differences in the YAP and Ki-67 immunoexpression levels among various group lesions. The correlation between those two proteins in individual groups was tested by Spearman correlation. A p-value of less than 0.05 was considered statistically significant. SPSS software version 25.0 was used.<\/jats:p><jats:p>There was a strong nuclear staining of YAP in basal and superficial cells and an intense cytoplasmic YAP positivity in odontogenic keratocysts, whereas a weaker YAP staining in both the nucleus and cytoplasm throughout the epithelial thickness was observed in dentigerous cyst, radicular cyst, and normal oral mucosa, respectively. YAP expression differed significantly in all odontogenic cysts compared with normal oral mucosa (p\u2009&lt;\u20090.05). Ki-67 expression was notably higher in odontogenic keratocysts relative to other cysts and normal oral mucosa. Although no statistically significant correlation was found between YAP and Ki-67 across the groups, both proteins displayed similar positive trends in odontogenic keratocysts.<\/jats:p><jats:p>These findings suggest that YAP activation may be related to the proliferative behavior of odontogenic cysts, especially in more aggressive lesions, but less likely to influence the inflammatory cysts. This insight could improve understanding of their pathogenesis and pave the way for new diagnostic and therapeutic approaches.<\/jats:p>","DOI":"10.1055\/s-0044-1801275","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T18:36:03Z","timestamp":1746124563000},"page":"1063-1070","source":"Crossref","is-referenced-by-count":0,"title":["YAP Expression is Related to the Aggressive Behavior of Odontogenic Cysts"],"prefix":"10.1055","volume":"19","author":[{"given":"Jutamas","family":"Uttagomol","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adjabhak","family":"Wongviriya","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariya","family":"Chantaramanee","sequence":"additional","affiliation":[{"name":"Department of Preventive Dentistry, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thanit","family":"Prasitsak","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, Faculty of Dentistry, Naresuan University, Phitsanulok, Thailand"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,5,1]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.devcel.2010.09.011","article-title":"The hippo signaling pathway in development and cancer","volume":"19","author":"D Pan","year":"2010","journal-title":"Dev Cell"},{"issue":"03","key":"ref2","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.devcel.2008.01.006","article-title":"The TEAD\/TEF family of transcription factor Scalloped mediates Hippo signaling in organ size control","volume":"14","author":"L Zhang","year":"2008","journal-title":"Dev Cell"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1152\/physrev.00005.2014","article-title":"The biology of YAP\/TAZ: Hippo signaling and beyond","volume":"94","author":"S Piccolo","year":"2014","journal-title":"Physiol Rev"},{"issue":"10","key":"ref4","first-page":"1674","article-title":"Integrin signalling regulates YAP and TAZ to control skin homeostasis","volume":"143","author":"A Elbediwy","year":"2016","journal-title":"Development"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1158\/1541-7786.MCR-14-0580","article-title":"A YAP\/TAZ-regulated molecular signature is associated with oral squamous cell carcinoma","volume":"13","author":"S E Hiemer","year":"2015","journal-title":"Mol Cancer Res"},{"issue":"67","key":"ref6","doi-asserted-by":"crossref","first-page":"111130","DOI":"10.18632\/oncotarget.22666","article-title":"Clinical significance of YAP1 activation in head and neck squamous cell carcinoma","volume":"8","author":"Y G Eun","year":"2017","journal-title":"Oncotarget"},{"issue":"14","key":"ref7","doi-asserted-by":"crossref","first-page":"4060","DOI":"10.7150\/ijbs.63305","article-title":"The Hippo pathway: a renewed insight in the craniofacial diseases and hard tissue remodeling","volume":"17","author":"J Chen","year":"2021","journal-title":"Int J Biol Sci"},{"issue":"05","key":"ref8","doi-asserted-by":"crossref","first-page":"2389","DOI":"10.1007\/s00784-018-2693-6","article-title":"Yes-associated protein (YAP) molecule expression in odontogenic epithelium of ameloblastoma","volume":"23","author":"R Anand","year":"2019","journal-title":"Clin Oral Investig"},{"issue":"01","key":"ref9","doi-asserted-by":"crossref","first-page":"49","DOI":"10.4103\/jomfp.jomfp_215_23","article-title":"Immunohistochemical evaluation of yes-associated protein molecule in the odontogenic epithelium of different histopathological variants of ameloblastoma and unicystic ameloblastoma","volume":"28","author":"B Pattnaik","year":"2024","journal-title":"J Oral Maxillofac Pathol"},{"key":"ref10","volume-title":"Odontogenic cysts and tumors.'in' Gnepp DR and Bishop JA.Gnepp's Diagnostic Surgical Pathology of the Head and Neck","author":"V I Woo","year":"2021","edition":"third ed."},{"key":"ref11","volume-title":"Odontogenic cysts 'in' Oral pathology","author":"S B Woo","year":"2023","edition":"thrid ed."},{"issue":"01","key":"ref12","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.cden.2019.08.002","article-title":"Odontogenic cysts","volume":"64","author":"A B Rajendra Santosh","year":"2020","journal-title":"Dent Clin North Am"},{"volume-title":"Odontogenic tumours. WHO classification of Head and Neck Tumors","year":"2005","author":"L Barnes","key":"ref13"},{"issue":"04","key":"ref14","doi-asserted-by":"crossref","first-page":"262","DOI":"10.7150\/ijms.4243","article-title":"Keratocystic odontogenic tumors: predictive factors of recurrence by Ki-67 and AgNOR labelling","volume":"9","author":"F Selvi","year":"2012","journal-title":"Int J Med Sci"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"66","DOI":"10.34172\/joddd.2021.012","article-title":"Ki-67 expression as a diagnostic biomarker in odontogenic cysts and tumors: a systematic review and meta-analysis","volume":"15","author":"M Jabbarzadeh","year":"2021","journal-title":"J Dent Res Dent Clin Dent Prospect"},{"issue":"01","key":"ref16","doi-asserted-by":"crossref","first-page":"36","DOI":"10.4103\/ejd.ejd_54_17","article-title":"Comparison of osteoclastogenesis and local invasiveness of ameloblastoma and keratocystic odontogenic tumor","volume":"12","author":"N H Al-Rawi","year":"2018","journal-title":"Eur J Dent"},{"issue":"03","key":"ref17","first-page":"138","article-title":"[Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ER-ICA) in breast cancer tissue]","volume":"8","author":"W Remmele","year":"1987","journal-title":"Pathologe"},{"issue":"01","key":"ref18","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s12253-014-9789-3","article-title":"Expression of human papillomavirus is correlated with Ki-67 and COX-2 expressions in keratocystic odontogenic tumor","volume":"21","author":"M A Alsaegh","year":"2015","journal-title":"Pathol Oncol Res"},{"issue":"01","key":"ref21","first-page":"16","article-title":"Multifaceted regulation and functions of YAP\/TAZ in tumors (Review)","volume":"40","author":"H Liu","year":"2018","journal-title":"Oncol Rep"},{"issue":"08","key":"ref22","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1242\/dev.102376","article-title":"The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease","volume":"141","author":"X Varelas","year":"2014","journal-title":"Development"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"1651","DOI":"10.1016\/j.cub.2018.04.018","article-title":"Dynamic fluctuations in subcellular localization of the Hippo Pathway Effector Yorkie in vivo","volume":"28","author":"S A Manning","year":"2018","journal-title":"Curr Biol"},{"issue":"04","key":"ref24","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/nrc3458","article-title":"The Hippo pathway and human cancer","volume":"13","author":"K F Harvey","year":"2013","journal-title":"Nat Rev Cancer"},{"issue":"21","key":"ref25","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1101\/gad.1602907","article-title":"Inactivation of YAP oncoprotein by the Hippo pathway is involved in cell contact inhibition and tissue growth control","volume":"21","author":"B Zhao","year":"2007","journal-title":"Genes Dev"},{"issue":"11","key":"ref26","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1016\/j.humpath.2008.04.012","article-title":"Expression of Yes-associated protein in common solid tumors","volume":"39","author":"A A Steinhardt","year":"2008","journal-title":"Hum Pathol"},{"issue":"07","key":"ref27","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.cell.2006.05.030","article-title":"Identification and validation of oncogenes in liver cancer using an integrative oncogenomic approach","volume":"125","author":"L Zender","year":"2006","journal-title":"Cell"},{"issue":"07","key":"ref28","doi-asserted-by":"crossref","first-page":"e45809","DOI":"10.15252\/embr.201845809","article-title":"YAP and TAZ are essential for basal and squamous cell carcinoma initiation","volume":"19","author":"M Debaugnies","year":"2018","journal-title":"EMBO Rep"},{"key":"ref29","first-page":"4624890","article-title":"Expression of YAP\/TAZ in keratocystic odontogenic tumors and its possible association with proliferative behavior","volume":"2017","author":"Q W Man","year":"2017","journal-title":"Biomed Res Int"},{"issue":"07","key":"ref30","doi-asserted-by":"crossref","first-page":"4538","DOI":"10.1111\/odi.14882","article-title":"Does YAP influence cell proliferation and apoptosis in benign epithelial odontogenic lesions?","volume":"30","author":"R IC Gon\u00e7alo","year":"2024","journal-title":"Oral Dis"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1111\/j.1600-0714.1975.tb01738.x","article-title":"The pathogenesis of odontogenic cysts: a review","volume":"4","author":"R M Browne","year":"1975","journal-title":"J Oral Pathol"},{"issue":"04","key":"ref32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1368-8375(01)00066-5","article-title":"The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 2. Proliferation and genetic studies","volume":"38","author":"M Shear","year":"2002","journal-title":"Oral Oncol"},{"issue":"01","key":"ref33","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1046\/j.1354-523X.2003.00974.x","article-title":"A comparative study of epithelial cell proliferation between the odontogenic keratocyst, orthokeratinized odontogenic cyst, dentigerous cyst, and ameloblastoma","volume":"10","author":"W Thosaporn","year":"2004","journal-title":"Oral Dis"},{"issue":"03","key":"ref34","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/S1368-8375(01)00065-3","article-title":"The aggressive nature of the odontogenic keratocyst: is it a benign cystic neoplasm? Part 1. Clinical and early experimental evidence of aggressive behaviour","volume":"38","author":"M Shear","year":"2002","journal-title":"Oral Oncol"},{"issue":"05","key":"ref35","doi-asserted-by":"crossref","first-page":"766","DOI":"10.7150\/ijms.29995","article-title":"Immunohistochemistry of YAP and dNp63 and survival analysis of patients bearing precancerous lesion and oral squamous cell carcinoma","volume":"16","author":"S Ono","year":"2019","journal-title":"Int J Med Sci"},{"issue":"04","key":"ref36","first-page":"103","article-title":"The hippo pathway in human upper gastrointestinal dysplasia and carcinoma: a novel oncogenic pathway","volume":"37","author":"D M Lam-Himlin","year":"2006","journal-title":"Int J Gastrointest Cancer"},{"issue":"06","key":"ref37","first-page":"1391","article-title":"Increased \u0394Np63 expression is predictive of malignant transformation in oral epithelial dysplasia and poor prognosis in oral squamous cell carcinoma","volume":"39","author":"R Matsubara","year":"2011","journal-title":"Int J Oncol"},{"issue":"01","key":"ref38","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/j.cell.2014.06.013","article-title":"YAP\/TAZ incorporation in the \u03b2-catenin destruction complex orchestrates the Wnt response","volume":"158","author":"L Azzolin","year":"2014","journal-title":"Cell"},{"issue":"01","key":"ref39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s00784-018-2421-2","article-title":"Immunohistochemical evaluation of Sonic Hedgehog signaling pathway proteins (Shh, Ptch1, Ptch2, Smo, Gli1, Gli2, and Gli3) in sporadic and syndromic odontogenic keratocysts","volume":"23","author":"A M Hoyos Cadavid","year":"2019","journal-title":"Clin Oral Investig"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"1200061","DOI":"10.3389\/fnins.2023.1200061","article-title":"A comprehensive review of stroke-related signaling pathways and treatment in western medicine and traditional Chinese medicine","volume":"17","author":"B Chen","year":"2023","journal-title":"Front Neurosci"}],"container-title":["European Journal of Dentistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0044-1801275.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T22:34:25Z","timestamp":1759530865000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0044-1801275"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,1]]},"references-count":38,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2025,10,3]]},"published-print":{"date-parts":[[2025,10]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0044-1801275","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["1305-7456","1305-7464"],"issn-type":[{"type":"print","value":"1305-7456"},{"type":"electronic","value":"1305-7464"}],"subject":[],"published":{"date-parts":[[2025,5,1]]}}}