CLONAL ANALYSIS OF SOLITARY INTRADUCTAL PAPILLOMA OF THE BREAST BY MEANS OF POLYMERASE CHAIN-REACTION

Clonality of solitary intraductal papillomas of the breast was analyze d using a method based on restriction fragment length polymorphism of the X-chromosome-linked phosphoglycerokinase (PGK) gene and on random inactivation of the gene by methylation. The application of polymerase chain reaction to this method enabled clonal analysis of such a small intraductal lesion as papilloma. Clonal analysis of DNA samples obtai ned from the nine solitary intraductal papillomas and adjacent normal breast tissues showed that all of the papillomas were monoclonal and a ll the normal breast tissues were polyclonal in origin. When DNA sampl es were obtained from four widely separated sites in the papillomas, c lonal analysis showed that all were monoclonal and, in addition, the s ame allele of PGK gene was inactivated in each case. These results dem onstrate that solitary intraductal papilloma arises as a single monocl onal tumor and extends along the ducts rather than occurring as multic entric monoclonal tumors and merging together subsequently. Immunohist ochemical staining of smooth muscle alpha-actin, a marker protein of m yoepithelial cells, revealed that solitary intraductal papilloma was c omposed of approximately equal mixtures of luminal epithelial and myoe pithelial cells. Since solitary intraductal papillomas were shown to b e monoclonal in origin, it was suggested that this disease originates from a common precursor that could differentiate into both luminal epi thelial and myoepithelial cells.