CORRELATION OF TRISOMY-12 WITH PROLIFERATING CELLS BY COMBINED IMMUNOCYTOCHEMISTRY AND FLUORESCENCE IN-SITU HYBRIDIZATION IN CHRONIC LYMPHOCYTIC-LEUKEMIA

Conventional G-banding and fluorescence in situ hybridization (FISH) w ere performed on peripheral blood samples of 340 consecutive untreated cases of chronic lymphocytic leukemia (CLL) for the detection of tris omy 12 and other chromosome abnormalities. These findings were correla ted with the proliferative activity of CLL lymphocytes assessed by the monoclonal antibody Ki-67. Cytogenetic analysis displayed a normal ka ryotype in 131 (38.5%) cases, trisomy 12 in 68 (20%), 31 by G-banding and an additional 37 cases by FISH, other clonal abnormalities in 47 ( 14%), and no metaphases in 94 (27.5%). The percentage of Ki-67-positiv e cells was significantly higher in cases with trisomy 12 (4.1 +/- 4.4 8) than in cases with a normal karyotype (1.5 +/- 2.0), those with oth er clonal abnormalities (1.35 +/- 1.37) and cases with no metaphases ( 1.14 +/- 1.6) (P < 0.0001). Cases with trisomy 12 were associated with more advanced clinical stage, atypical morphology and a higher percen tage of Ki-67+ve cells than cases lacking trisomy 12 (P < 0.0001). Alt hough there was no direct correlation between the percentage of trisom ic and proliferating cells, the combination of immunocytochemistry and FISH showed that most Ki-67-positive cells were trisomic for chromoso me 12. Our results suggest that the association of trisomy 12 with a h igher proliferative activity supports the view that this abnormality i s a secondary event associated with disease progression in CLL.