ABSTRACT
The proto-oncogene (pleomorphic adenoma gene 1 (PLAG1)) is immunohistochemically overexpressed in pleomorphic adenoma (PA). Its expression in recurrent pleomorphic adenoma (RPA), however, has not been investigated. Since complex mechanisms are involved in tumor recurrence, the aim of this study was to investigate whether PLAG1 overexpression occurs in RPA. We studied PLAG1 protein expression in 40 PAs and 36 RPAs by immunohistochemistry. Cases with immunopositive cells were classified into two categories, between 10 and 50 % and >50 %. In both groups, PLAG1 expression was observed in both epithelial and myoepithelial cells. Of PAs, 37 cases (93 %) were positive, while this was the case in 34 RPA cases (94 %). Our findings suggest that in addition to morphological similarity, PA and RPA express PLAG1, which might play a role in tumor recurrence. Furthermore, as for PA, expression of PLAG1 can be considered a valuable diagnostic marker for RPA.
Subject(s)
Adenoma, Pleomorphic/metabolism , Adenoma, Pleomorphic/pathology , DNA-Binding Proteins/metabolism , Salivary Gland Neoplasms/metabolism , Adenoma, Pleomorphic/diagnosis , Adult , Aged , DNA-Binding Proteins/genetics , Female , Humans , Immunohistochemistry/methods , In Situ Hybridization, Fluorescence/methods , Male , Middle Aged , Proto-Oncogene Mas , Recurrence , Salivary Gland Neoplasms/diagnosis , Salivary Gland Neoplasms/pathology , Transcription Factors/geneticsABSTRACT
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.
