title: Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma.
abstract: PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.
authors.affiliation: Pathology Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Beatriz Samara
authors.initials: BS
authors.lastname: de Brito
authors.affiliation: Pathology Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Natália
authors.initials: N
authors.lastname: Giovanelli
authors.affiliation: Pathology Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Erika Said
authors.initials: ES
authors.lastname: Egal
authors.affiliation: Oral Pathology Department, Piracicaba Dental School, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Celeste
authors.initials: C
authors.lastname: Sánchez-Romero
authors.affiliation: Oral Pathology Department, Piracicaba Dental School, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Juliana de Souza do
authors.initials: JS
authors.lastname: Nascimento
authors.affiliation: Head and Neck Surgery Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Antonio Santos
authors.initials: AS
authors.lastname: Martins
authors.affiliation: Head and Neck Surgery Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Álfio José
authors.initials: ÁJ
authors.lastname: Tincani
authors.affiliation: Head and Neck Surgery Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Del Negro
authors.affiliation: Pathology Department, Federal University of Santa Catarina (UFSC), Florianópolis, SC 88040-900, Brazil.
authors.forename: Rogério de Oliveira
authors.initials: RO
authors.lastname: Gondak
authors.affiliation: Oral Pathology Department, Piracicaba Dental School, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Oslei Paes de
authors.initials: OP
authors.lastname: Almeida
authors.affiliation: Head and Neck Surgery Department, AC Camargo Cancer Center, São Paulo, SP 01509-010, Brazil.
authors.forename: Luiz Paulo
authors.initials: LP
authors.lastname: Kowalski
authors.affiliation: Pathology Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil.
authors.forename: Albina
authors.initials: A
authors.lastname: Altemani
authors.affiliation: Pathology Department, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP 13083-887, Brazil. Electronic address: fevimariano@gmail.com.
authors.forename: Fernanda Viviane
authors.initials: FV
authors.lastname: Mariano
mesh_terms: D008949:Adenoma, Pleomorphic / Q000737:chemistry* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002471:Cell Transformation, Neoplastic / Q000737:chemistry* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D012468:Salivary Gland Neoplasms / Q000737:chemistry* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C104382:PLAG1 protein, human
keywords: Carcinogenesis; Carcinoma ex pleomorphic adenoma; Immunohistochemistry; Malignant transformation; PLAG1; Pleomorphic adenoma