p53 abnormalities in splenic lymphoma with villous lymphocytes

The incidence and role of p53 abnormalities have not been reported in splen ic Lymphoma with villous lymphocytes (SLVL), the leukemic counterpart of sp lenic marginal zone lymphoma. Because p53 abnormalities correlate with prog ressive and refractory disease in cancer and isochromosome 17q has been des cribed in SLVL, a low-grade lymphoma that behaves aggressively in a minorit y of patients, this study investigated p53 changes by molecular and immunop henotypic methods in samples from 59 patients. The p53 deletion was analyze d by fluorescence in situ hybridization, and p53 protein expression was ass essed by immunocytochemistry in 35 of 59 cases and by flow cytometry in 20 of 35 patients. Ten patients (17%) had a monoallelic p53 loss, 3 (9%) of 35 nuclear protein expression by immunocytochemistry, and 2 (10%) of 20 by fl ow cytometry, Two patients had both deletion and protein expression. Direct sequencing of all p53 exons was used to delineate mutations in 9 of 11 pat ients with an identified abnormality. Mutations, both compromising p53 DNA binding, were identified in the 2 patients with deletion and protein accumu lation. Kaplan-Meier analysis revealed a significantly worse survival for p atients with p53 abnormalities. Although p53 abnormalities are infrequent i n SLVL, they underlie a more aggressive disease course and poor prognosis, (Blood, 2001; 97:3552-3558) (C) 2001 by The American Society of Hematology.