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p53 Expression in B-Cell Chronic Lymphocytic Leukemia: A Marker of
Disease Progression and Poor Prognosis
Iole Cordone,
Serena Masi,
Francesca Romana Mauro,
Silvia Soddu,
Ornella Morsilli,
Tiziana Valentini,
Maria Luce Vegna,
Cesare Guglielmi,
Francesca Mancini,
Sonia Giuliacci,
Ada Sacchi,
Franco Mandelli, and
Robert Foa
From the Dipartimento di Biotecnologie Cellulari ed Ematologia,
Università "La Sapienza," Rome; Dipartimento di Scienze
Biomediche ed Oncologia Umana, Università di Torino,
Torino; and Laboratorio di Oncogenesi Molecolare, Istituto
Regina Elena, Rome, Italy.
We have analyzed by immunocytochemistry (ICC) the frequency of p53
protein expression in 181 cases of B-cell chronic lymphocytic leukemia
(CLL) followed at a single institution to assess the relationship
between p53 and the clinical and morphological features of the disease,
as well as the possible involvement of this protein in the pathogenesis
of the more aggressive forms of CLL. The overall frequency of p53
protein positivity in CLL was 15% (27 of 181 cases). There were no
significant differences in age, sex, absolute lymphocyte count, or
lymphocyte doubling time between p53-positive and -negative patients.
By contrast, p53-positive patients had a significantly higher
percentage of prolymphocytes (P = .002) and a significantly
lower percentage of residual CD3-positive T lymphocytes (P = .0001). No correlation was found between the percentage of p53-positive
cells and the percentage of cells in cycle assessed by the monoclonal
antibody Ki-67. When the percentage of p53 positivity was correlated
with the clinical stage of the disease, the proportion of p53-positive
cases increased significantly from Binet's stage A (8 of 108; 7.4%),
to stage B (12 of 49; 24.4%) and C (7 of 24; 29.2%) (P = .002). p53 positivity correlated also with the phase of the disease,
showing a low expression at diagnosis (8 of 112; 7.1%) and a
significantly higher expression in patients studied during the course
of the disease (7 of 35; 20%) and, to a further extent, with disease
progression (12 of 34; 35.3%) (P = .0001). The association
of p53 protein expression with mutations in the gene was confirmed by
direct sequence of the entire cDNA in 15 of the 17 ICC positive cases
tested (88%). A significantly shorter treatment-free interval from
diagnosis (P = .003) and a poorer response to therapy
(P = .007) was observed in p53-positive compared with
p53-negative patients. Overall survival from the time of diagnosis, as
well as from the time of p53 protein analysis, was significantly
shorter in patients with p53 protein expression (P = .03 and
.0001, respectively). Moreover, in multivariate analysis, p53
expression and stage C were independently associated with a short
survival. The results of this study indicate that in CLL the expression
of the p53 protein, analyzed by a simple and reliable immunocytochemical method, is strongly associated with p53 gene mutations, a morphological variant (CLL with >10%
prolymphocytes), advanced clinical stage, progressive
disease, poor response to therapy, and short survival.
Blood, Vol. 91 No. 11 (June 1), 1998:
pp. 4342-4349
© 1998 by The American Society of Hematology.
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