| Abstrakt: |
Kinetic index determined by enumeration of neoplastic cells positive for proliferative cell nuclear antigen (PCNA) in 70 breast carcinomas (avidin-biotin immunoperoxidase technique) was compared to synthesis-phase fraction (S-phase, or SPF) values obtained by flow cytometry (FCM) using a multiparametric, 2 color method (dual-label propidium iodide/cytokeratin-FITC). The percent PCNA positive tumor cells (12.5% mean, range 1–28%) was significantly greater in aneuploid tumors (14.2% mean, N=35) compared to diploid range tumors (10.7% mean, N=35) (p<0.05), and was correlated with SPF derived from ungated DNA histograms (12.5% mean ± 5.5%, r=0.45, p<0.001). Marginally stronger statistical correlations were observed between the PCNA index and SPF values calculated from cytokeratin-gated (15.8% mean, r=0.53, p<0.001) DNA histograms or from SPF values obtained following linear baseline debris subtraction (mean=8.1%, r=0.48, p<0.001). Significant associations were identified between PCNA index and prognostically important clinicopathologic parameters including nuclear grade (p=0.014), presence of necrosis (p=0.005), and angiolymphatic invasion (p=0.003). We conclude: 1) PCNA index is comparable to FCM SPF and correlates with factors of known prognostic importance in carcinoma of the breast; 2) baseline debris and contaminating events derived from non-epithelial cells both represent significant artifacts in proliferative fraction estimates derived from FCM DNA histograms; and 3) multiparametric analysis may represent one means of improving the specificity and clinical value of FCM SPF determinations. |
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