{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:18:07Z","timestamp":1758845887468,"version":"3.44.0"},"reference-count":39,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T00:00:00Z","timestamp":1620000000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010438","name":"Poznan University of Medical Sciences","doi-asserted-by":"crossref","award":["502-14-11081320-11154"],"award-info":[{"award-number":["502-14-11081320-11154"]}],"id":[{"id":"10.13039\/501100010438","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2021,4,7]]},"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>The aim of the study is to correlate p16<jats:sup>Ink4a<\/jats:sup> expression with the clinical courses of pleomorphic adenoma (PA), its malignant transformation (CaexPA) and treatment outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Retrospective analysis (1998\u20132019) of 47 CaexPA, 148\u2009PA and 22 normal salivary gland samples was performed. PAs were divided into two subsets: clinically \u2018slow\u2019 tumours characterised by stable size or slow growth; and \u2018fast\u2019 tumours with rapid growth rate.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Positive p16<jats:sup>Ink4a<\/jats:sup> expression was found in 68\u2009PA and 23 CaexPA, and borderline expression in 80 and 20, respectively. All 22 (100%) normal salivary gland samples presented with no p16<jats:sup>Ink4a<\/jats:sup> expression. Significant difference in p16<jats:sup>Ink4a<\/jats:sup> expression was observed between normal tissue, PA and CaexPA (\u03c7<jats:sup>2<\/jats:sup> (4)=172,19; p=0.0001). The PA clinical subgroups were also evaluated separately, revealing additional statistical relations: \u2018fast\u2019 PA and CaexPA differed significantly in p16Ink4a expression (\u03c7<jats:sup>2<\/jats:sup> (2)=8.06; p=0.01781) while \u2018slow\u2019 PA and CaexPA did not (\u03c7<jats:sup>2<\/jats:sup> (2)=3.09; p=0.2129). 3-year, 5-year and 10-year survival among p16<jats:sup>Ink4a<\/jats:sup> positive CaexPA patients was 100%, 90.56% and 60.37%, respectively, and in CaexPA patients with borderline p16<jats:sup>Ink4a<\/jats:sup> expression was 90.0%, 73.64% and 22.20%, respectively. Statistically significant difference between expression pattern and survival rate was observed (F Cox test \u2013 F (16, 24)=2.31; p=0.03075).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our study confirms no p16<jats:sup>Ink4a<\/jats:sup> expression in normal tissue, but reveals differences in expression between \u2018fast\u2019 and \u2018slow\u2019 PA. We suggest that p16<jats:sup>Ink4a<\/jats:sup> overexpression is connected to PA proliferation and subsequent malignant transformation to CaexPA. Borderline p16<jats:sup>Ink4a<\/jats:sup> staining correlates with worse prognosis of CaexPA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jclinpath-2021-207440","type":"journal-article","created":{"date-parts":[[2021,5,3]],"date-time":"2021-05-03T13:20:29Z","timestamp":1620048029000},"page":"605-611","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Expression of p16<sup>Ink4a<\/sup> protein in pleomorphic adenoma and carcinoma ex pleomorphic adenoma proves diversity of tumour biology and predicts clinical course"],"prefix":"10.1136","volume":"75","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3351-0923","authenticated-orcid":false,"given":"Ewelina","family":"Bartkowiak","sequence":"first","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Piwowarczyk","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Bodnar","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland"},{"name":"Department of Clinical Pathomorphology, Nicolaus Copernicus University in Toru\u0144 Ludwik Rydygier Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pawe\u0142","family":"Kosikowski","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jadzia","family":"Chou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aldona","family":"Wo\u017aniak","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ma\u0142gorzata","family":"Wierzbicka","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology and Laryngological Oncology, Poznan University of Medical Sciences, Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2021,5,3]]},"reference":[{"key":"2025092506005249000_75.9.605.1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.oraloncology.2017.01.004","article-title":"Salivary gland pleomorphic adenoma in the Netherlands: a nationwide observational study of primary tumor incidence, malignant transformation, recurrence, and risk factors for recurrence","volume":"66","author":"Valstar","year":"2017","journal-title":"Oral Oncol"},{"key":"2025092506005249000_75.9.605.2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12105-011-0281-z","article-title":"Carcinoma ex pleomorphic adenoma: a comprehensive review of clinical, pathological and molecular data","volume":"6","author":"Antony","year":"2012","journal-title":"Head Neck Pathol"},{"key":"2025092506005249000_75.9.605.3","doi-asserted-by":"crossref","first-page":"888","DOI":"10.1002\/lary.24964","article-title":"Etiology and management of recurrent parotid pleomorphic adenoma: management of recurrent pleomorphic adenoma","volume":"125","author":"Witt","year":"2015","journal-title":"Laryngoscope"},{"key":"2025092506005249000_75.9.605.4","doi-asserted-by":"publisher","DOI":"10.1016\/S0046-8177(82)80140-8"},{"key":"2025092506005249000_75.9.605.5","doi-asserted-by":"publisher","DOI":"10.1002\/path.1711460308"},{"key":"2025092506005249000_75.9.605.6","doi-asserted-by":"crossref","first-page":"29","DOI":"10.4103\/jomfp.JOMFP_74_17","article-title":"A mixed odontogenic sarcoma: a challenging histopathologic case and brief review of the literature","volume":"22","author":"Atarbashi-Moghadam","year":"2018","journal-title":"J Oral Maxillofac Pathol"},{"key":"2025092506005249000_75.9.605.7","doi-asserted-by":"crossref","first-page":"113","DOI":"10.4236\/ojpathology.2013.33020","article-title":"Pleomorphic adenoma with Exuberant squamous metaplasia and keratin cysts mimicking squamous cell carcinoma in minor salivary gland","volume":"03","author":"Lim","year":"2013","journal-title":"OJPathology"},{"key":"2025092506005249000_75.9.605.8","doi-asserted-by":"crossref","DOI":"10.3389\/fonc.2020.600707","article-title":"Salivary gland pleomorphic adenomas presenting with extremely varied clinical courses. 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