Molecular evidence that the stromal and epithelial cells in pleomorphic adenomas of salivary gland arise from the same origin: Clonal analysis using human androgen receptor gene (HUMARA) assay

Salivary gland pleomorphic adenomas are characterized by a biphasic growth of "epithelial" and "stromal" regions. The "epithelial" region is a compact ly organized mixture of both luminal and nonluminal cells, whereas the stro mal region is composed predominantly of the nonluminal cells. Using the pol ymerase chain reaction (PCR)-based HUMARA assay on DNA from formalin-fixed, paraffin-embedded tissues from pleomorphic adnomas of female patients, we intend to clarify the clonal relation between the luminal and nonluminal ce lls and the clonal nature of the morphologically diverse nonluminal cells i n this tumor. HUMARA, the human androgen receptor gene, is located on the X chromosome and contains a segment of polymorphic CAG tandem repeats in exo n 1. Several methylation-sensitive HhaI restriction sites are located 5' to these CAG repeats. It is an ideal tool to study clonality of female tissue s by examining the methylation pattern. Of the 13 cases analyzed, 3 were ho mozygous at the HUMARA locus and therefore noninformative. The remaining 10 cases were informative. All 10 cases showed a monoclonal pattern in the st romal area, indicating that the morphologically diverse nonluminal cells ar e monoclonal. Eight of the 10 cases showed monoclonality in the "epithelial " areas, suggesting a common clonality between luminal and nonluminal cells . Of the remaining 2 samples, I was polyclonal for the "epithelial" region, and the other was not amplifiable. Our data provide the first molecular ev idence that the luminal and nonluminal cells in pleomorphic adenomas arise from the same clone in most cases, and the morphologically diverse nonlumin al cells are monoclonal. HUM PATHOL 31:498-503. Copyright (C) 2000 by W.B. Saunders Company.