Article
Lab Invest 2001, 81:1289–1297
Histologic Localization of PLAG1 (Pleomorphic Adenoma Gene 1) in Pleomorphic Adenoma of the Salivary Gland: Cytogenetic Evidence of Common Origin of Phenotypically Diverse Cells
This work was supported by the Geconcerteerde Onderzoekacties 1997–2001, the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (FWO), and the Belgian program on Interuniversity Poles of Attraction initiated by the Belgian State, Prime Minister's Office, Science Policy Programming. MLV is a Chercheur Qualifie from the Fonds National de la Recherche Scientifique. IVV is a doctoral fellow of the FWO.
Maria Debiec-Rychter1,5, Isabelle Van Valckenborgh2,4,5, Christel Van den Broeck3, Anne Hagemeijer1, Wim J M Van de Ven2, Koen Kas2, Boudewijn Van Damme3 and Marianne L Voz2
- 1Laboratory for Cytogenetics and Molecular Genetics of Human Malignancies, Center for Human Genetics, Katholieke Universiteit Leuven, Leuven, Belgium
- 2Laboratory for Molecular Oncology, Center for Human Genetics, Katholieke Universiteit Leuven and Flanders Interuniversity Insitute for Biotechnology, Leuven, Belgium
- 3Department of Pathology, Katholieke Universiteit Leuven, Leuven, Belgium
- 4Department of Otorhinolaryngology, Head and Neck Surgery, Katholieke Universiteit Leuven, Leuven, Belgium
Correspondence: Dr. Maria Debiec-Rychter, Center for Human Genetics, Katholieke Universiteit Leuven, Herestraat 49, B-3000 Leuven, Belgium. E-mail: maria.debiec-rychter@med.kuleuven.ac.be
5MD-R and IVV contributed equally to this report.
Received 6 June 2001.
Abstract
Pleomorphic adenoma gene 1 (PLAG1), a zinc finger transcription factor gene, is consistently rearranged and overexpressed in human pleomorphic adenomas of the salivary glands with 8q12 translocations. In this report, we describe the immunohistochemical localization of PLAG1 protein in pleomorphic adenomas of the salivary gland and corresponding normal tissue, in relation to cytokeratin, vimentin, and BCL-2 expression. Normal salivary gland tissue was not immunoreactive for PLAG1. In primary pleomorphic adenomas, cells strongly immunoreactive for PLAG1 were detected in the outer layer of tubulo-ductal structures, which are thought to be the origin of cells with bi-directional, epithelial, and mesenchymal phenotypes. In contrast, epithelial cells with abundant cytokeratin in the inner tubulo-ductal structures only sporadically expressed PLAG1. BCL-2 immunoreactivity was found mainly in the cells surrounding the tubulo-ductal structures and in the solid undifferentiated cellular masses, within the areas that had moderate PLAG1 immunoreactivity. The variability of PLAG1 expression in neoplastic cells seemed to reflect the morphologic heterogeneity that correlated with the stage of differentiation of the tumor cells. Immunohistochemical/cytogenetic evaluation of two pleomorphic adenomas with t(3;8)(p21;q12) or t(5;8)(p13;q12) translocations demonstrated the clonal nature of immunophenotypically diverse cells. This finding confirms the theory that pleomorphic adenoma cells share a common single-cell origin, most likely from the epithelial progenitor basal duct cells.
