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Blood, 1 June 2001, Vol. 97, No. 11, pp. 3552-3558
NEOPLASIA
p53 abnormalities in splenic lymphoma with villous
lymphocytes
Alicja M. Gruszka-Westwood,
Rifat A. Hamoudi,
Estella Matutes,
Esperanza Tuset, and
Daniel Catovsky
From the Academic Department of Haematology and
Cytogenetics, Institute of Cancer Research/Royal Marsden NHS Trust,
London, United Kingdom; and Cancer Gene Cloning Centre, Institute of
Cancer Research, Sutton, United Kingdom.
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.
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