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The expression of p53 protein in non-Hodgkin's lymphomas is not always
dependent on p53 gene mutations
R Villuendas, MA Piris, P Algara, M Sanchez-Beato, L Sanchez-Verde, JC Martinez, JL Orradre, P Garcia, C Lopez and P Martinez
Department of Genetics, Virgen de la Salud Hospital, Toledo, Spain.
p53 overexpression has been found to be a fairly common feature in high
grade lymphomas in the majority of tumoral cells. The results vary from
series to series, from 25% to 33% of cases. To assess whether
immunohistochemical positivity for p53 correlated with the presence of
structural gene abnormalities, DNA from 16 non-Hodgkin's lymphomas with
high and low p53 values was amplified and sequenced to determine the
existence of point mutations in the highly conserved regions of the p53
gene. In the group of 8 cases containing high levels of protein, 3 cases
showed missense point mutations at the codons mapping between exons 5
through 8. Of the 8 cases of tumors containing undetectable or low levels
of p53 protein, 1 case presented a nonsense point mutation giving a stop
codon. No missense mutations were detected in this group. The finding of
p53 mutations in 4 of 16 cases confirms the presence of p53 gene mutations
in high grade lymphomas distributed over different histologic groups. These
include Burkitt's lymphoma, together with centroblastic, immunoblastic, and
large cell lymphoma of mucosa origin. Nevertheless, the absence of
mutations in 5 of the 8 cases that overexpressed p53 suggests that the
nuclear or cytoplasmic stabilization of p53 protein could also depend on
other factors. The absence of detectable levels of p53 protein cannot
discount the existence of p53 mutations, as is shown by a case of Burkitt's
lymphoma in which a nonsense mutation was detected. The impact of this
range of p53 alterations on clinical course and treatment response of the
patients deserves to be explored, in an attempt to differentiate the
specific consequences of each one.
Volume 82,
Issue 10,
pp. 3151-3156,
11/15/1993
Copyright © 1993 by The American Society of Hematology
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