Loss Expression of Plag1 in Malignant Transformation from Pleomorphic Adenoma to Carcinoma Ex-Pleomorphic Adenoma

• Published in: Human pathology Vol. 57; pp. 152 - 159
• Main Authors: de Brito, Beatriz Samara, Giovanelli, Natália, Egal, Erika Said Abu, DVM, Romero-Sanchez, Celeste, DDS, MsC, de Souza, Juliana Nascimento, DDS, MsC, Martins, Antonio Santos, MD, PhD, Tincani, Álfio José, MD, PhD, Del Negro, André, MD, PhD, de Almeida, Oslei Paes, DDS, PhD, Kowalski, Luiz Paulo, MD, PhD, Altemani, Albina, MD, PhD, Mariano, Fernanda Viviane, DDS, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2016; Elsevier Limited
• Subjects: Adenoma, Pleomorphic - chemistry; Adenoma, Pleomorphic - pathology; Biomarkers, Tumor - analysis; Carcinogenesis; Carcinoma - chemistry; Carcinoma - pathology; Carcinoma ex pleomorphic adenoma; Case-Control Studies; Cell Differentiation; Cell Transformation, Neoplastic - chemistry; Cell Transformation, Neoplastic - pathology; Disease Progression; DNA-Binding Proteins - analysis; Down-Regulation; Female; Genes; Humans; Immunohistochemistry; Male; Malignant transformation; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Pathology; PLAG1; Pleomorphic adenoma; Proteins; Salivary Gland Neoplasms - chemistry; Salivary Gland Neoplasms - pathology; Tumorigenesis; Tumors; immunohistochemistry; PLAG1; Pleomorphic adenoma; Carcinoma ex pleomorphic adenoma; Immunohistochemistry; Carcinogenesis; Malignant transformation
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2016.07.011

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 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 histopathological subtype of CXPA. Forty PA, 21 residual PA (without malignant transformation) and forty CXPA were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a two-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according histopathological subtype and invasiveness degree. Thirty seven PA (92.5%), fifteen residual PA (71%) and fourteen CXPA (35%) were positive for PLAG1. According CXPA group: 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 pathways activation and different clone cells. Additionally, PLAG1 expression seems to be present mainly in low grade carcinomas and in cases with early phase of invasion, due 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 as hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.