HETEROGENEITY IN RENAL-CELL CARCINOMA AND ITS IMPACT ON PROGNOSIS - AFLOW CYTOMETRIC STUDY

In the process of tumour progression genetic instability is the basis for the evolution of tumour cell clones with various genotypic and phe notypic characteristics causing heterogeneity. Renal cell carcinoma ha s a long prediagnostic growth period, which increases the probability of clonal evolution. We have studied 200 consecutive renal cell carcin omas, addressing the interrelationship between intratumour heterogenei ty and clinicopathological factors. DNA ploidy patterns were analysed in multiple samples from each tumour using flow cytometry and compared with clinical stage, tumour invasion, metastatic rate and survival. E ighty-five of 192 evaluable tumours (44%) were homogeneous concerning DNA ploidy (62% diploid, 38% aneuploid). Among 107 heterogeneous tumou rs a majority (79%) contained aneuploid as well as diploid cell clones . Homogeneously diploid tumours had a lower incidence of local tumour spread compared with tumours with aneuploid cell clones (P < 0.001), b ut the frequency of distant metastasis at time of diagnosis was simila r. The presence of aneuploidy in at least one sample from a tumour was a significant adverse prognostic factor (P < 0.001), whereas the degr ee of heterogeneity had no influence on survival. The frequent heterog eneity demonstrated indicates that multiple samples must be investigat ed to evaluate properly the malignant character of renal cell carcinom a.