TP53 deletions but not trisomy 12 are adverse in B-cell lymphoproliferative disorders

Abnormalities of the TP53 tumor suppressor gene at 17p13.1 are prognostical ly adverse in a variety of hematolymphoid malignancies. The present study u tilized interphase fluorescence in situ hybridization (I-FISH) to detect TP 53 deletions and trisomy 12 in 101 clinical specimens from 98 patients with B-cell lymphoproliferative disorders (B-LPDs). Twelve patients had TP53 de letions (group A), 23 had trisomy 12 (group B), and 63 had neither(group C) . The groups did not significantly differ in age, duration of disease, abso lute lymphocyte count, or percentage with an immunophenotype or cytology at ypical for chronic lymphocytic leukemia (CLL). The clinical stage of diseas e and lactate dehydrogenase (LDH) level were higher in group A, with less r esponse to therapy. After a median follow-up of 19 months, seven of the pat ients in group A had died of disease (another patient subsequently has had large cell transformation) compared with none in group B and nine in group C. Multivariate analysis found the stage of disease and TP53 deletions as t he only parameters independently associated with shortened survival (P < 0. 001). Thirty-nine patients had conventional cytogenetic analysis (CCA) whic h was complexly abnormal in 11 patients; 6 of whom died of disease. There w as a trend for complex cytogenetics to be seen more frequently in group A, often with 17p involvement. For most laboratories, CCA may be the preferabl e initial study to identify prognostically different subgroups of B-LPDs. H owever, as more probes and clinical outcome data become available, I-FISH w ill likely play an increasingly important ancillary role. (C) 2000 Elsevier Science Inc. All rights reserved.