{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T02:09:57Z","timestamp":1762826997187,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006181","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado da Bahia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006181","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Oral Pathology Medicine"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Purpose<\/jats:title>\n \n Polymorphous adenocarcinoma of the salivary gland is characterized by cellular uniformity associated with a variety of morphological growth patterns, a fact that makes its diagnosis challenging. Therefore, the identification of genetic alterations and signaling pathways emerges as a tool for elucidation of the pathogenesis of this tumor and accurate differential diagnosis. The aim of this study was to assess mutations in the\n \n PRKD1<\/jats:italic>\n <\/jats:styled-content>\n gene and in protein components of the\n HH<\/jats:styled-content>\n pathway (\n SHH<\/jats:styled-content>\n ,\n IHH<\/jats:styled-content>\n ,\n SMO<\/jats:styled-content>\n , and\n GLI<\/jats:styled-content>\n \u20101) in cases of polymorphous adenocarcinoma of the salivary gland.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Sanger sequencing was used to interrogate hotspot mutations in\n \n PRKD1<\/jats:italic>\n <\/jats:styled-content>\n exon 15 and immunohistochemistry to analyze the protein expression of\n PRKD1<\/jats:styled-content>\n ,\n SHH<\/jats:styled-content>\n ,\n IHH<\/jats:styled-content>\n ,\n SMO<\/jats:styled-content>\n , and\n GLI<\/jats:styled-content>\n \u20101.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n \n PRKD1<\/jats:italic>\n <\/jats:styled-content>\n c.\n 2130A<\/jats:styled-content>\n >C\/T hotspot mutation was detected in 50% of the sequenced samples. A previously unreported variant, c.\n 2110C<\/jats:styled-content>\n >T resulting in p.\n His704Tyr<\/jats:styled-content>\n , was identified in one case, while 100% of the samples carried the intronic variation rs2273813, regardless of tissue invasion (perineural, lymphovascular, fat, bone, muscle, and mucous acini). Immunostaining revealed significant results for several associations between\n PRKD1<\/jats:styled-content>\n ,\n IHH<\/jats:styled-content>\n ,\n SMO<\/jats:styled-content>\n , and\n GLI<\/jats:styled-content>\n \u20101. In contrast,\n SHH<\/jats:styled-content>\n immunoexpression did not correlate with the expression of the other proteins.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n The\n \n PRKD1<\/jats:italic>\n E710D\n <\/jats:styled-content>\n hotspot mutation and protein expression of\n PRKD1<\/jats:styled-content>\n and\n HH<\/jats:styled-content>\n components (\n SHH<\/jats:styled-content>\n ,\n IHH<\/jats:styled-content>\n ,\n SMO<\/jats:styled-content>\n , and\n GLI<\/jats:styled-content>\n \u20101) were detected in\n PAC<\/jats:styled-content>\n regardless of tissue invasion, although\n HH<\/jats:styled-content>\n proteins contributed to the morphogenesis of this rare oral cancer. Additionally, the positive correlation between the expression of\n PRKD1<\/jats:styled-content>\n and\n HH<\/jats:styled-content>\n pathway components (\n IHH<\/jats:styled-content>\n ,\n SMO<\/jats:styled-content>\n , and\n GLI<\/jats:styled-content>\n \u20101) suggests a possible interaction between these proteins, independent of the\n HH<\/jats:styled-content>\n pathway ligand.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/jop.70057","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T01:49:52Z","timestamp":1757555392000},"page":"1053-1061","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hedgehog Components Are Present in Polymorphous Adenocarcinoma of the Salivary Gland Regardless of\n \n PRKD1<\/i>\n <\/scp>\n Mutation and Tissue Invasion"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9060-2907","authenticated-orcid":false,"given":"Dandara Andrade","family":"De Santana","sequence":"first","affiliation":[{"name":"Postgraduate Program in Dentistry and Health, School of Dentistry Universidade Federal da Bahia Salvador Bahia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-5530-1699","authenticated-orcid":false,"given":"Cec\u00edlia Vit\u00f3ria Lima","family":"De Oliveira","sequence":"additional","affiliation":[{"name":"School of Dentistry Federal University of Bahia Salvador Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-6503","authenticated-orcid":false,"given":"Fl\u00e1via Cal\u00f3 De Aquino","family":"Xavier","sequence":"additional","affiliation":[{"name":"Postgraduate Program in Dentistry and Health, School of Dentistry Universidade Federal da Bahia Salvador Bahia Brazil"},{"name":"Laboratory of Oral and Maxillofacial Pathology, School of Dentistry Universidade Federal da Bahia Salvador Bahia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8662-5965","authenticated-orcid":false,"given":"Manoela Domingues","family":"Martins","sequence":"additional","affiliation":[{"name":"School of Dentistry, Department of Oral Pathology Universidade Federal do Rio Grande do Sul \u2013 UFRGS Porto Alegre Rio Grande do Sul Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6083-4218","authenticated-orcid":false,"given":"Bruno Cunha","family":"Pires","sequence":"additional","affiliation":[{"name":"Centro de Diagn\u00f3stico Pires Feira de Santana Bahia Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6147-6307","authenticated-orcid":false,"given":"Tercio 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