Cell kinetics in human breast cancer: comparison between the prognostic value of the cytofluorimetric S-phase fraction and that of the antibodies to Ki-67 and PCNA antigens detected by immunocytochemistry

The determination of cell proliferation is one of the more widely used tools for assessing prognosis. However, additional research in this field is warranted because today there are several methodological procedures available for monitoring cell kinetics and it has still not been established which is the most reliable marker of proliferation and which possesses the greatest prognostic value. We performed this study in a series of primary invasive breast cancers to compare the prognostic value of S-phase fraction (SPF) by flow cytometry, the most widely used method for detecting proliferation at present, with that of antibodies to Ki-67 and PC-10 to proliferating-cell nuclear antigen (PCNA) detected by immunocytochemical methods. A significant linear relationship was observed only between SPF and Ki-67. In univariate analysis SPF and Ki-67 values, nodal status, histological grading and peritumoral lymphatic-vessel invasion were significant predictors of relapse- free survival (RFS). As far as overall survival (OS) is concerned, only SPF, Ki-67 and nodal status were significantly associated with the risk of death. PCNA had no prognostic value for either RFS or OS. In multivariate analysis only SPF and nodal status retained a significant and independent prognostic value. Neither the cell-kinetics parameters assessed by immunocytochemistry (i.e. Ki-67 and PCNA) nor histological grading were independent prognosticators. In conclusion, our results provide evidence that the determination of SPF by flow cytometry was the strongest cell-kinetics marker used to assess prognosis in this series of breast cancers. However, different and novel markers of cell kinetics need to be compared in larger series in order to identify the best one.