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.