Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma

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de Brito, Beatriz Samara ; Giovanelli, Natalia ; Egg, Erika Said ; Sanchez-Romero, Celeste ; do Nascimento, Juliana de Souza ; Martins, Antonio Santos ; Tincani, Alfio Jose ; Del Negro, Andre ; Gondak, Rogerio de Oliveira ; de Almeida, Oslei Paes ; Kowalski, Luiz Paulo ; Altemani, Albina ; Mariano, Fernanda Viviane

• Document type: Journal article
• Source: HUMAN PATHOLOGY; v. 57, p. 152-159, NOV 2016.
• Web of Science Citations: 9

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. (C) 2016 Elsevier Inc. All rights reserved. (AU)

• FAPESP's process: 14/18312-1 - Analysis of PLAG1 expression in pleomorphic adenoma and carcinoma ex pleomorphic adenoma
• Grantee: Beatriz Samara de Brito
• Support type: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 11/23204-5 - Genomic profile study of carcinoma ex-pleomorphic adenoma by array-comparative genomic hybridization
• Grantee: Albina Messias de Almeida Milani Altemani
• Support type: Regular Research Grants
• FAPESP's process: 11/23366-5 - Genomic profile study of carcinoma ex-pleomorphic adenoma by array-comparative genomic hybridization
• Grantee: Fernanda Viviane Mariano Brum Corrêa
• Support type: Scholarships in Brazil - Post-Doctorate