DNA-FLOW CYTOMETRY (PLOIDY AND S-PHASE FRACTION) AS PROGNOSTIC FACTORIN A RETROSPECTIVE SERIES OF 515 PRIMARY BREAST-CANCER

Paraffin-embedded tissues are used in retrospective studies to evaluat e the prognostic significance of DNA-flow cytometry (DNA-FCM) in human breast cancer. Although paraffin-embedded samples yield information o n disease-free survival (DFS) and overall survival (GAS) of homogeneou sly selected patients, the resulting DNA-histograms have a lower resol ution of aneuploid subpopulations and higher debris levels than those of fresh tumor samples. The aim of this study was to evaluate, retrosp ectively, the prognostic value of ploidy and the S-phase fraction (SPF ) using 515 samples of paraffin-embedded consecutive primary breast ca ncer tissue (median follow-up: 75.4 months). Ploidy was detectable in 89% cases (34% diploid and 66% aneuploid) and SPF in 77%. The optimal cut-off for SPF was 6%. High SPF values were significantly correlated with shorter DFS (p=0.028) and OAS (p=0.018); aneuploidy was significa ntly correlated only with a shorter OAS (p=0.0058). Using the Cox prop ortional hazards regression model to evaluate the independence of DNA- FCM derived parameters, only high SPF was able to predict both a short er DFS (p=0.02) and OAS (p=0.002). Furthermore, high SPF values were f ound correlated to aneuploidy (p<0.00001), tumor necrosis (p<0.015) an d high histopathological grade (p<0.03). The data reported confirm tha t SPF is a valuable single independent prognostic factor in human brea st, cancer and strongly support the use of archival tumor specimens to study the prognostic role of DNA-FCM in human cancer.