title: p53 abnormalities in splenic lymphoma with villous lymphocytes.
abstract: The incidence and role of p53 abnormalities have not been reported in splenic lymphoma with villous lymphocytes (SLVL), the leukemic counterpart of splenic marginal zone lymphoma. Because p53 abnormalities correlate with progressive and refractory disease in cancer and isochromosome 17q has been described in SLVL, a low-grade lymphoma that behaves aggressively in a minority of patients, this study investigated p53 changes by molecular and immunophenotypic methods in samples from 59 patients. The p53 deletion was analyzed by fluorescence in situ hybridization, and p53 protein expression was assessed 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 flow cytometry. Two patients had both deletion and protein expression. Direct sequencing of all p53 exons was used to delineate mutations in 9 of 11 patients with an identified abnormality. Mutations, both compromising p53 DNA binding, were identified in the 2 patients with deletion and protein accumulation. Kaplan-Meier analysis revealed a significantly worse survival for patients with p53 abnormalities. Although p53 abnormalities are infrequent in SLVL, they underlie a more aggressive disease course and poor prognosis. (Blood. 2001;97:3552-3558)
authors.affiliation: Academic Department of Haematology and Cytogenetics, Institute of Cancer Research/Royal Marsden NHS Trust, Fulham Rd., London, SW3 6JJ United Kingdom.
authors.forename: A M
authors.initials: AM
authors.lastname: Gruszka-Westwood
authors.forename: R A
authors.initials: RA
authors.lastname: Hamoudi
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.forename: E
authors.initials: E
authors.lastname: Tuset
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D017353:Gene Deletion; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000737:chemistry*; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA; D013156:Splenectomy; D013160:Splenic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D016159:Tumor Suppressor Protein p53 / Q000032:analysis
chemical_list: D016159:Tumor Suppressor Protein p53