Cytogenetic studies of normal kidney tissue and renal cell carcinoma

Abstract: In the present thesis normal kidney tissue and renal cell carcinoma (RCC) were studied by cytogenetic and fluorescence in situ hybridization (FISH) methods to investigate chromosomal aberrations. In the first study, 4 samples of nonneoplastic kidney tissue were cultured for cytogenetic analysis and trisomy 7 was found in all cases in 3-15% of the cells. In the second study, cytogenetic analysis of 30 RCC showed that +7 was rarely present together with clonal structural abnormalities, in particular 3p changes, making it highly unlikely that trisomy 7 represents a primary change in RCC. In the third study, nonneoplastic kidney tissue was cultured for 4-46 days and the frequency of trisomy 7 showed no consistent variation during the culturing period studied. In the fourth study, FISH of interphase nuclei was performed in uncultured nonneoplastic kidney tissues and showed that the frequency of +7 varied between 1.0-9.0% of the cells. Combination of FISH with immunostaining with CD3 for T-lymphocytes and cytokeratins for epithelial cells showed that, in all samples, the cells with +7 found in nonneoplastic kidney tissue were epithelial in 20-75% and T-lymphocytes in only 0-5%. Among freshly isolated renal cells, in the fifth study, trisomy 7 was observed mainly in proximal tubular cells positive for brush-border antigen, and, to a lesser extent, in distal tubular cells positive for Tamm-Horsfall glycoprotein. The frequency of trisomy 7 in lymphocytes expressing CD3 or CD22 isolated from nonneoplastic and tumor tissues was substantially lower than in the epithelial cells and was not increased compared with the frequency in control lymphocytes from peripheral blood. These results thus demonstrate that the nonneoplastic kidney cells with trisomy 7 are mainly of epithelial origin, preferentially of the proximal tubule. In the final study, 50 consecutive patients with RCC were followed for a median of 4.2 years. There was a significant association between the degree of cytogenetic complexity and survival, in that patients with five or less aberrations had a better prognosis than those with more than five changes. Patients with del(8p)/-8, +12, and +20 had a significantly worse prognosis compared with those without these aberrations, but +7 had no impact on prognosis.