Proliferation Rate in Different Cell Types in Benign Breast Disease

Abstract

The histological patterns of Benign Breast Disease (BBD) are related to structural interaction of different cell types i.e. epithelial, myoepithelial, apocrine and “null” undifferentiated cells.

To identify the type of the proliferating cell, we devised a dual immunostaining procedure: the proliferating nuclei were labelled by 5-bromo-2′-deoxyuridine (BrdU) and/or PCNA (cyclin) and stained in brown with an immunoperoxidase reaction, while we employed alkaline phosphatase anti-alkaline phosphatase (APAAP) (red staining) or, alternatively, β-galactosidase (blu staining) procedures to visualize specific cytoplasmic markers. Luminal epithelial cells were identified by a monoclonal antibody against keratin (AE1); myoepithelial cells were specifically recognized by α-sm-actin antibody and apocrine cells were stained by serum directed against GCDFP-15, a glycoprotein of cystic disease fluid. Cells unstained by these antibodies were defined “null” or undifferentiated. Fifteen cases of BBD were studied and different lobular lesions (epitheliosis, blunt duct adenosis, sclerosing adenosis and apocrine cysts) were identified in H&E stained sections. On serial sections stained with the double immunocytochemical procedure the different cell types constituting the lesions were counted. Within each cytotype, the absolute and relative number of proliferating cells was evaluated.

The results indicate that apocrine cells in cystic lesions do not proliferate representing therefore terminally differentiated cells. In typical ductal “hyperplasia” (epitheliosis) and in sclerosing adenosis, proliferation was negligible in all type of cells.

We conclude that terms such as ductal or lobular “hyperplasia” are misnomers; we could not confirm the hypothesis that these processes represent precursors to highly proliferative carcinomatous lesions.