Cell cycle analysis of 932 flow cytometric DNA histograms of fresh frozen breast carcinoma material. Correlations between flow cytometric, clinical, and pathologic variables. MMMCP Collaborative Group. Multicenter Morphometric Mammary Carcinoma Project Collaborative Group.

Abstract

Confusing data have been presented for breast cancer patients on correlations between DNA ploidy and the percentage of S-phase cells and other prognostic variables. The aim of this study was to compare DNA ploidy classification and cell cycle variables with clinical, classic, and quantitative pathologic variables and clinical variables in a large group of patients. DNA ploidy and cell cycle variables were extracted from MultiCycle (Phoenix Flow Systems, San Diego, CA) interpreted flow cytometric DNA histograms of fresh frozen material from 932 breast cancer patients and compared with clinical (age, hormonal status), classic pathology (lymph node status, tumor size and type), and quantitative pathologic variables (steroid receptor status, mitotic activity index [MAI], mean nuclear area [MNA]). The DNA ploidy correlated significantly with MAI, MNA steroid receptor status, and tumor type. No significant correlations were found with tumor size, lymph node status, age, and hormonal status. The first DNA index correlated significantly with MAI, MNA, and steroid receptor status. The percentage of S-phase cells significantly correlated with MAI, MNA, steroid receptor status, and lymph mode status. DNA index and DNA ploidy, as markers of genetic instability, correlated well with differentiation and proliferation markers and less well with lymph node status and tumor size as markers of metastatic potential and duration of disease. The percentage of S-phase cells was not independent of the percentage of differentiation markers and did not correlate strongly with mitotic activity. This indicates that the percentage of S-phase cells and the mitotic activity partially reflect different proliferative properties.