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The accumulation of p53 abnormalities is associated with progression of
mucosa-associated lymphoid tissue lymphoma
M Du, H Peng, N Singh, PG Isaacson and L Pan
Department of Histopathology, University College London Medical School, UK.
The genetic mechanisms underlying the genesis of low-grade mucosa-
associated lymphoid tissue (MALT) lymphomas and their transformation into
high-grade lymphoma are poorly understood. p53 inactivation, commonly
caused by mutation and allele loss, has been shown to play an important
role in the early development and/or the late disease progression of many
human tumors including lymphoid malignancies and, thus, may also be
important in MALT lymphomagenesis. We examined 75 cases (48 low grade and
27 high grade) of MALT lymphoma for p53 allele loss and mutation as well as
protein accumulation. DNA samples prepared from microdissected cell
populations were used for the detection of p53 gene abnormalities. Loss of
heterozygosity (LOH) of the gene was detected by polymerase chain
reaction-based analysis of p53 CA repeat polymorphism, whereas p53 mutation
was studied by single-strand conformation polymorphism analysis and direct
sequencing. p53 expression was assessed by immunostaining with CM1
polyclonal antibody. p53 allele loss and mutation, which resulted in the
alteration in the amino acid sequence, were found in both low-grade (LOH, 3
of 44 [6.8%]; mutation, 9 of 48 [18.8%]) and high-grade (LOH, 6 of 21
[28.6%]; mutation, 9 of 27 [33.3%]) MALT lymphomas, particularly in the
latter group. p53 staining was not observed in any low-grade tumors but in
6 high-grade cases that harbored missense mutations. There were also
differences in the extent of p53 abnormalities, between low- and high-
grade tumors. Of the 11 low-grade tumors showing p53 abnormalities, only 1
tumor showed the concomitance of p53 mutation and allele loss, whereas in
high-grade tumors, 6 of 9 affected cases displayed both p53 mutation and
allele loss. Our results suggest that p53 partial inactivation may play an
important role in the development of low-grade MALT lymphomas, whereas
complete inactivation may be associated with high-grade transformation.
Volume 86,
Issue 12,
pp. 4587-4593,
12/15/1995
Copyright © 1995 by The American Society of Hematology
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