Clonal analysis of benign and malignant human breast tumors by means of polymerase chain reaction.

Clonal analysis was conduced on a variety of benign and malignant human breast tumors using the method based on restriction fragment length polymorphism (RFLP) of the X 120 chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. Breast carcinoma was shown to be monoclonal in origin, consistent with a somatic mutational theory. Precancerous lesions such as atypical ductal hyperplasia and multiple intraductal papilloma were also found to be monoclonal, indicating that certain genetic changes had been accumulated in these lesions. Solitary intraductal papilloma was found to be monoclonal. Since this tumor is composed of two types of cells, luminal epithelial cells and myoepithelial cells, it was suggested that the origin of solitary intraductal papilloma is a precursor cell which is capable of differentiating into both luminal and myoepithelial cells. The fact that fibroadenoma is polyclonal indicates that this tumor is not neoplasia but hyperplasia of a lobule. Epithelial component of phyllodes tumor was found to be polyclonal but stromal component was found to be monoclonal. Thus, phyllodes tumor is considered to be a neoplasm of stromal cells but not of epithelial cells.