CELL-CYCLE ANALYSIS OF NORMAL, ATROPHIC, AND HYPERPLASTIC BREAST EPITHELIUM USING 2-COLOR MULTIPARAMETRIC FLOW-CYTOMETRY

We performed two-color flow cytometric synthesis phase fraction (SPF) determinations on cytokeratin-labeled benign epithelial populations fr om 142 breast specimens (41 mastectomy, 70 diagnostic biopsy, 31 reduc tion mammoplasty). There was wide variability of SPF, ranging from 0.1 to 3.5%, with a frequency distribution skewed to higher values (mean 0.75%, median 0.5%). The mean SPF for women less than 29 years was 0.9 1%, vs. 0.89% for 30-42 years, 0.66% for 43-49 years, and 0.56% for gr eater than or equal to 50 years (P = 0.05). Histologically atrophic ti ssue samples exhibited a mean SPF approximately half that of morpholog ically normal tissue from premenopausal age women (0.79% vs. 0.36%, P = 0.02). Tissues showing: histologically proliferative fibrocystic fea tures had a greater mean SPF than non-proliferative fibrocystic tissue s (0.59% vs. 0.92%); however, due to the wide spread of values within each of these categories, this difference was not statistically signif icant and neither group was significantly different from 'normal' tiss ue samples. Patients with histologically normal breast tissue, though, were significantly younger (mean = 34.6 years) than those with fibroc ystic changes (non-proliferative mean = 53.4 years vs. proliferative m ean = 42.8 years, P = 0.005). Synchronous right- and left-sided specim ens obtained from reduction mammoplasty demonstrated significantly cor related SPF determinations (R = 0.77). We conclude that selective anal ysis of epithelial populations using two-color flow cytometry provides cell cycle information in benign breast tissue which is analogous to that obtained by labor-intensive nucleotide labeling studies. This stu dy also confirms the biologic variability and age-dependence of breast epithelial proliferation. Finally, the data imply that derangements o f cell proliferation in fibrocystic conditions are heterogeneous, comp lex and incompletely correlated with histologic parameters such as hyp erplasia. Copyright (C) 1996 Elsevier Science Ireland Ltd.