Diagnostic Utility of PLAG1 Immunohistochemical Determination in Salivary Gland Tumors

Abstract

PLAG1 (pleomorphic adenoma gene 1) is a proto-oncogene whose overexpression is a crucial oncogenic event in salivary gland pleomorphic adenomas (PA), and in carcinoma ex-PA. The aim of the present study is to evaluate the sensitivity and the specificity of PLAG1 as a marker in the differential diagnosis of salivary gland benign and malignant tumors. We examined 101 cases, including 36 PAs, 8 myoepitheliomas, 3 basal cell adenomas, and 1 canalicular adenoma among benign tumors; 16 mucoepidermoid carcinomas, 10 adenoid cystic carcinomas, 8 acinic cell carcinomas, 8 polymorphous low-grade adenocarcinomas, 7 salivary duct carcinoma, and 4 epithelial-myoepithelial carcinoma among malignant tumors. PLAG1 was diffusely positive in 94.4% of PAs and in all myoepitheliomas, although with a lower staining intensity. Among malignant tumors, 2 (25%) polymorphous low-grade adenocarcinomas and 1 salivary duct carcinoma ex-PA were positive. In conclusion, PLAG1 is a marker with good specificity for PA and could be a useful diagnostic adjunct in the diagnosis of salivary gland tumors. In particular, this marker is negative in the most common salivary carcinomas, including adenoid cystic carcinoma, mucoepidermoid carcinoma, and acinic cell carcinoma. However, some mimickers of PA, like polymorphous low-grade adenocarcinoma, may show occasional positivity for PLAG1, thus limiting its diagnostic use. In addition, carcinoma ex-PA shows consistent positivity, and therefore should be considered as a diagnostic possibility in case of a malignant tumor with PLAG1 expression.