Histologic localization of PLAG1 (pleomorphic adenoma gene 1) in pleomorphic adenoma of the salivary gland: Cytogenetic evidence of common origin of phenotypically diverse cells

Pleomorphic adenoma gene 1 (PLAG1), a zinc finger transcription factor gene , is consistently rearranged and overexpressed in human pleomorphic adenoma s of the salivary glands with 8q12 translocations. In this report, we descr ibe the immunohistochemical localization of PLAG1 protein in pleomorphic ad enomas of the salivary gland and corresponding normal tissue, in relation t o cytokeratin, vimentin, and BCL-2 expression. Normal salivary gland tissue was not immunoreactive for PLAG1. In primary pleomorphic adenomas, cells s trongly immunoreactive for PLAG1 were detected in the outer layer of tubulo -ductal structures, which are thought to be the origin of cells with bi-dir ectional, epithelial, and mesenchymal phenotypes. In contrast, epithelial c ells with abundant cytokeratin in the inner tubulo-ductal structures only s poradically expressed PLAG1. BCL-2 immunoreactivity was found mainly in the cells surrounding the tubulo-ductal structures and in the solid undifferen tiated cellular masses, within the areas that had moderate PLAG1 immunoreac tivity. The variability of PLAG1 expression in neoplastic cells seemed to r eflect the morphologic heterogeneity that correlated with the stage of diff erentiation of the tumor cells. lmmunohistochemical/cytogenetic evaluation of two pleomorphic adenomas with t(3;8)(p21;q12) or t(5;8)(p13;q12) translo cations demonstrated the clonal nature of immunophenotypically diverse cell s. This finding confirms the theory that pleomorphic adenoma cells share a common single-cell origin, most likely from the epithelia[ progenitor basal duct cells.